brazilianpropolis

Ubi apis ibi salus “Wherever there are bees there is health” Caio Plinio Secondo 23 - 79 A.D.

REGISTER INTEREST IN POSSIBLE SEMINARS email info@brazilianpropolis.org
with your name, profession, complete professional contact details and preferred seminar date.

Supported by Angelsweb Innovation http://www.angelsweb.biz http://www.brazilianpropolis.org

A series of free educational seminars for health professionals by:-

Prof Dr Niraldo Paulino, PhD (1)
Dr Ellen Silveira, MD, PhD, (2)
Dr Gerson Machado, DIC PhD (3)

Evening events - Imperial College, London
Registration 18:30, talks from 19:00 to 21:00

Saturday all day event - Imperial College, London
Registration 09:30, talks from 10:00 to 15:15

Location: Imperial College London, South Kensington Campus, London SW7 2AZ
Lecture Theatre in the Skempton Building – Underground South Kensington

Travelling and location directions.pdf

Seminar details: seminar details oct 06.pdf

http://www.google.co.uk/search?q=propolis+cancer+japan+&hl=en&lr=&start=50&sa=N

PROPOLIS WHAT IS IT?

Propolis Research Table of Contents

Propolis Description	Therapeutic Properties of propolis
History of Use of propolis		Antimicrobial Effects
Production and Consumption		Anticancer Effects
Composition of propolis		Antioxidant Effects
Human Nutrition		Wound Healing and Tissue Repair Effects
Clinical Effects on Humans		Anaesthetic Effects
Adverse Effects		Effects on Immune System
Commercial Use of propolis		Cardiovascular Effects
Food Safety		Dental Care Effects
Quality Control

Propolis starts as the sticky resinous sap which seeps from the buds of certain trees and oozes from the bark of others. The bees gather this "bee glue" and carry it back to the hive where it is blended with wax flakes secreted from special glands on the underside of the bees abdomen. Propolis is used to line the interior of brood cells in preparation for the Queens laying of eggs. With its antiseptic properties it provides a hospital clean environment for the rearing of brood. Propolis is a very complex mixture that varies according to the source it comes from. At least 180 different compounds have been identified so far in propolis. A broad analysis reveals approximately 55% resinous compounds and balsams, 30% beeswax, 10% ethereal and aromatic oils, and 5% bee pollen. Many flavonoids contribute to propolis and have a great deal to do with its antibacterial qualities. Other components include cinnamic acid, cinnamyl alcohol, vanillin, caffeic acid, tectochrysin, isalpinin,, pinocembrin, chrysin, galangin, and ferulic acid.

Research shows that propolis offers antiseptic, antibiotic, anti-fungal, and even antiviral properties. It is often called "Russian Penicillin" in acknowledgement of the extensive research that has been done by the Soviets. One of the most valuable properties of all the natural bee hive products is that they exhibit true immunostimulating characteristics. Unlike many modern medical drugs, propolis does not depress the immune system, but instead boosts it. Chemical antibiotics destroy all bacteria in the body including the friendly and necessary flora required for healthy functioning. An individual that takes constantly takes antibiotics for one condition after another soon learns that the drugs no longer work as well as they once did. As the bacteria get "smarter" the drugs become less effective over time. It is a medical fact that some biologically harmful strains of bacteria develop a resistance to antibiotics. Propolis, being a natural antibiotic works against harmful bacteria without destroying the friendly bacteria your body needs. Propolis has been proven effective against some strains of bacteria that resist chemical antibiotics.

Propolis is collected by commercial beekeepers, either by scraping the substance from wooden hive parts, or by using specially constructed collection mats. The raw product undergoes secondary processing to remove beeswax and other impurities before being used in a variety of natural health care products (eg., lozenges, tinctures, ointments, toothpaste).

Propolis is derived from the Greek works pro ("before") and polis ("city"), and refers to the observation made by beekeepers in ancient times that bees often built a wall of propolis at the front entrance of their colony.

Propolis has been used by man since early times, for various purposes, and especially as a medicine because of its antimicrobial properties (Crane, 1997). Ancient Greek texts refer to the substance as a "cure for bruises and suppurating sore", and in Rome propolis was used by physicians in making poultices. The Hebrew word for propolis is tzori, and the therapeutic properties of tzori are mentioned throughout the Old Testament. Records from 12th century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, and dental caries.

One of the non-medicinal uses of propolis is as a varnish, and it has been suggested that the special properties of Stradivarius violins may be partly due to the type of propolis used, although the claim cannot be substantiated.

Anticancer Effects
Ethanol extracts of propolis have been found to transform human hepatic and uterine carcinoma cells in vitro, and to inhibit their growth (Matsuno, 1992). Substances isolated in propolis which produce this cytotoxic effect are quercetin, caffeic acid, and clerodane diterpendoid. Clerodane diterpendoid shows a selective toxicity to tumour cells.

Propolis was also found to have a cytotoxic and cytostatic effect in vitro against hamster ovary cancer cells and sarcoma-type tumours in mice (Ross, 1990). The substance has also displayed cytotoxicity on cultures of human and animal tumour cells, including breast carcinoma, melanoma, colon, and renal carcinoma cell lines. (Grunberger et al, 1988). The component producing these effects was identified as caffeic acid phenethy ester.

A substance called Artepillin C has been isolated from propolis, and has been shown to have a cytotoxic effect on human gastric carcinoma cells, human lung cancer cells and mouse colon carcinoma cells in vitro (Kimoto, et al, 1995).

Antioxidant Effects
The flavonoids concentrated in propolis are powerful antioxidants, and have been shown to be capable of scavenging free radicals and thereby protecting lipids and other compounds such as Vitamin C from being oxidised or destroyed (Popeskovic, et al, 1980). It is probable that active free radicals, together with other factors, are responsible for cellular ageing and degradation in such conditions as cardiovascular diseases, arthritis, cancer, diabetes, Parkinson disease and Alzheimer disease.

Wound Healing and Tissue Repair Effects
Propolis has been shown to stimulate various enzyme systems, cell metabolism, circulation and collagen formation, as well as improve the healing of burn wounds (Ghisalberti, 1979; Krell, 1996). These effects have been shown to be the result of the presence of arginine in propolis (Gabrys, et al, 1986). Propolis and aloe vera was found to be superior to standard wound treatment products in trials on mice (Sumano-Lopez, et al, 1989).

Anaesthetic Effects
Propolis and some of its components produce anaesthesia, which in some studies has been shown to be 3 times as powerful as cocaine and 52 times that of procaine, when tested in rabbit cornea (Ghisalberti, 1979). The anaesthetic effect has been shown to be produced by pinocembrin, pinostrobin, caffeic acid esters components in propolis (Paintz and Metzner, 1979).

The anaesthetic effect may explain why propolis has been used for centuries in the treatment of sore throats and mouth sores. An anaesthetising ointment for dentistry using propolis has been patented in Europe (Sosnowski, 1984).

Effects on Immune System
Propolis has been shown to stimulate an immune response in mice (Manolova, et al, 1987). More recently, Japanese researchers have shown an extract of propolis to produce a macrophage activation phenomenon related to the immune function in humans (Moriyasu, et al, 1993). Propolis activates immune cells which produce cytokines. The results help to explain the anti-tumour effect produced by propolis.

Propolis has been shown to suppress HIV-1 replication and modulate in vitro immune responses, and, according to the authors, "May constitute a non-toxic natural product with both anti-HIV-1, and immunoregulatory effects" (Harish, et al, 1997).

Cardiovascular Effects
In mice, a concentrated extract of propolis has been shown to reduce blood pressure, produce a sedative effect, and maintain serum glucose (Kedzia et al, 1988). Dihydroflavonoids, as contained in propolis, have been shown to strengthen capillaries (Roger, 1988), and produce antihyperlipidemic activity (Choi, 1991). Propolis has also been shown to protect the liver against alcohol (ethanol) and tetrachloride in rats (Coprean, et al, 1986).

Dental Care Effects
In rats inoculated with S. sobrinus, about half of their fissures were carious, while dental caries were significantly less in rats given water containing propolis extract. No toxic effects of propolis on the growth of rats were observed under experimental conditions in this study (Ikeno, et al, 1991). Propolis has also been shown to be effective as a subsidiary treatment for gingivitis (gum infections) and plaque (Neumann, et al, 1986). A 50% propolis extract was found to antiseptic against pulp gangrene (Gafar, et al, 1986).

Clinical Effects on Humans
A total of 260 steel workers suffering from bronchitis were treated for 24 days by various methods including local and systemic regulation of the immune system and local treatment with an ethanol extract of propolis (EEP) in a physiological salt solution. Best results were obtained with inhalation of the extract, together with propolis tablets (Scheller et al, 1989a). Propolis has also shown positive effects in other otorhinolaryngologic diseases, such as pharyngitis (Doroshenko, 1975), chronic bronchitis (Scheller, et al, 1989a), rhinopharyngolaryngitis (Isakbaev, 1986), pharyngolaryngitis (Lin, et al, 1993), catarrh (Zommer-Urbanska et al, 1987), and rhinitis (Nunex, et al, 1988).
Sixty students were divided into groups to test the effect of propolis on the development of plaque and gingivitis. The results suggest that a propolis preparation can be a useful subsidiary treatment in oral hygiene (Neumann, et al, 1986).

A strong immune deficiency was found in 2 patients with alveolitis fibroticans. Treatment with a combination of the propolis, Esberitox N and calcium-magnesium resulted in good improvements in the state of the immune system and the clinical condition of both patients (Scheller et al, 1989 b).

Clinical applications of propolis (1-10%) in ether or alcohol were effective against 10 superficial fungi and 9 deep-growing fungi. On oral treatment of 160 psoriasis patients with 0.3 g propolis 3 times daily for 3 months, about one-third were cured or greatly improved (Fang Chu, 1978).

Patients (110) infected with ringworm were treated with 50% propolis as a unguent. In 97 patients it was found to produce excellent results (Bolshakova, 1975).

Sixty-four patients with tibial skin ulcers, aged from 23 to 98 years, were treated using propolis tincture in an ointment. The ointment was applied daily to the ulcerated area, which was also treated on the periphery with antibiotic ointments. The treatment lasted for 4-12 weeks. At the end of treatment, 19 of the 64 treated patients exhibited no clinical signs of the condition, 19 an improved condition (Korsun, 1983).

Patients (229) with burns, clean wounds, infected wounds or abscesses/ulcers were treated with a cream containing propolis at two concentrations (2% and 8%). The higher concentration caused local intolerance in 18% of patients by day 9, whereas the lower concentration caused symptoms in only 1.8% of patients by day 16. Burns and wounds treated with the low concentration cream healed in 11 days on average, septic wounds in 17.5 days, 67% of ulcers in 36 days (Morales and Garbarino, 1996).

Patients (126) suffering external otitis, chronic mesotypanic otitis and tympan perforation were treating with propolis solutions (5-10%). A positive therapeutic result was reported in most cases (Matel, et al, 1973). Propolis has also shown positive results in the treatment of acute inflammations of the ear (Palos, et al, 1989).

Patients (90) with cases of vagina and uterus cervix inflammation caused by S. pyogenes were treated with 3% propolis ethanol extract. Over 50% of the cases responded well to this treatment (Zawadzki and Scheller, 1973).

Patients (138) suffering giardiasis were treated with propolis extracts (10-20%). In children, 52% showed a cure at the lower dose. In adults, the cure rate was the same as for tinidazole, an antiprotozoan drug, at the 20% extract, and 60% vrs. 40% for tindazole at a higher concentration (30% propolis extract) (Mirayes, et al, 1988).

The diverse use of propolis in clinical trials shows that its therapeutic efficacy lies mainly in diseases caused by microbial contaminations (Marcucci, 1995).

Commercial Use
Raw propolis is collected by beekeepers and sold in bulk to companies that refine the product and turn it into usable extracts. Most commercial uses of propolis are based on preparations made up from these extracts. Methods include ethanol extraction (EEP), glycol extraction (GEP), aqueous (water) extraction (AEP), oil extraction (OEP), and water-soluble derivatives (WSD). Where solvents are used, reduction or elimination of the solvent is necessary, either by freeze-drying, vacuum distillation, or evaporation. Extraction is used to remove the beeswax which is mixed with the propolis by the bees during use in the hive, as well as other non-active components such as resinous-balsam substances.

Main commercial uses of propolis are as a dietary supplement and therapeutic. Propolis is sold in tablets (singularly, or in combination with other substances such as pollen, royal jelly and non-hive products), and tinctures, and as an ingredient in lozenges, skin creams, shampoos, lipsticks, toothpastes and mouthwashes. Tinctures and lozenges are popular treatment for sore throats, and tinctures are often used to treat cuts, mouth sores and skin rashes. The antioxidant, antimicrobial and antifungal activities of propolis also offer opportunities in food technology. In Japan, the use of propolis is permitted as a preservative in frozen fish (Krell, 1996).

Propolis is a stable product, but should nevertheless be stored in airtight containers in the dark, preferably away from excessive and direct heat. Propolis does not lose much of its antibiotic activity, even when stored for 12 months or longer. Propolis and its extract function as a mild preservative due to their antioxidant and antimicrobial activities and thus may actually prolong the shelf life of some products (Krell, 1996).

http://www.texasdrone.com/propolis.htm

http://ecam.oxfordjournals.org/cgi/content/abstract/nep024v1
CAM Advance Access published online on April 7, 2009
eCAM, doi:10.1093/ecam/nep024

© 2009 The Author(s).
This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits
unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.

Propolis and the Immune System: A Review

J.M. Sforcin * Department of Microbiology and Immunology, Biosciences Institute, UNESP, 18618-000 Botucatu, SP, Brazil

Abstract
Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. In recent years, in vitro and in vivo assays provided new information concerning its mechanisms of action, thus a review dealing with propolis and the immune system became imperative. This review compiles data from our laboratory as well as from other researchers, focusing on its chemical composition and botanical
sources, the seasonal effect on its composition and biological properties, its immunomodulatory and antitumor properties, considering its effects on antibody production and on different cells of the immune system, involving the innate and adaptive immune response. In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity. Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production was demonstrated. Propolis inhibitory effects on lymphoproliferation may be associated to its anti-inflammatory property. In immunological assays, the best results were observed when propolis was administered over a short-term to animals. Propolis antitumor property and its anticarcinogenic and antimutagenic potential are discussed. Since humans have used propolis for different purposes and propolis-containing products have been marketed, the knowledge of its properties with scientific basis is not only of academic interest but also of those who use propolis as well. This review opens a new perspective on the investigation
of propolis biological properties, mainly with respect to the immune system.

Keywords: Propolis; Immune system; Antitumor property

Contents
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. Propolis immunomodulatory action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1. Propolis action on macrophages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2. Propolis action on lymphocytes and antibody production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.3. Propolis’ antitumoral activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Abbreviations:
ACF, aberrant crypt foci; ADCC, antibody-dependent
cellular cytotoxicity; AST, aspartate aminotransferase; BSA, bovine serum
albumin; CAPE, caffeic acid phenethyl ester; Con A, concanavalin A; Erk-
2, extracellular-signal-regulated kinase; GC, gas-chromatography; GC–MS,
gas chromatography–mass spectrometry; H2O2, hydrogen peroxide; IFN-_,
gamma-interferon; IL, interleukin; KLH, keyhole limpet hemocyanin; MAP,
mitogen-activated protein; NK, natural killer cells; NO, nitric oxide; NOS, nitric
oxide synthase; O2
-, superoxide anion; OCl-, hypochlorite; OH•, hydroxyl
radical; PBMC, peripheral blood mononuclear cells; PHA, phytohemagglutinin;
SRBC, sheep red blood cells; TLC, thin layer chromatography; TGF-_1,
transforming growth factor-beta 1; TNF-_, tumor necrosis factor-alpha; TVT,
transmissible venereal tumor; WSD, water-soluble derivative
* Tel.: +55 14 3811 6058; fax: +55 14 3815 3744.
E-mail address: sforcin@ibb.unesp.br.

1. Introduction
Propolis has attracted researchers’ interest in the last decades
because of several biological and pharmacological properties,
such as immunomodulatory, antitumor, antimicrobial, antiinflammatory,
antioxidant, among others (Bankova et al., 2000).
Besides, propolis-containing products have been intensely marketed
by the pharmaceutical industry and health-food stores
(Banskota et al., 2001). The ethnopharmacological approach,
combined with chemical and biological methods, may provide
useful pharmacological leads. Thus, this reviewaimed to discuss
its chemical composition and plant sources as well

Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in
Tube-forming Endothelial Cells through Inactivation of Survival Signal
ERK1/2
Kazuhiro Kunimasa1,*, Mok-Ryeon Ahn,, Tomomi Kobayashi1, Ryoji
Eguchi2, Shigenori Kumazawa1, Yoshihiro Fujimori3, Takashi Nakano2,
Tsutomu Nakayama1, Kazuhiko Kaji1and Toshiro Ohta,*

Graduate School of Nutritional and Environmental Sciences and Global
COE Program, University of Shizuoka, Shizuoka 422-8526, 2Department of
Thoracic Oncology, Hyogo College of Medicine and 3Cancer Center, Hyogo
College of Medicine, Hyogo 663-8501, Japan

We recently reported that propolis suppresses tumor-induced angiogenesis
through tube formation inhibition and apoptosis induction in endothelial
cells. However, molecular mechanisms underlying such angiogenesis
suppression by propolis have not been fully elucidated. The aim of this
study was to investigate the effects of ethanol extract of Brazilian
propolis (EEBP) on two major survival signals, extracellular
signal-regulated kinase 1/2 (ERK1/2) and Akt, and to elucidate whether
changes in these signals were actually involved in antiangiogenic
effects of the propolis. Detection by western blotting revealed that
EEBP suppressed phosphorylation of ERK1/2, but not that of Akt.
Pharmacological inhibition by U0126 demonstrated that ERK1/2
inactivation alone was enough to inhibit tube formation and induce
apoptosis. It was also shown that EEBP and U0126 similarly induced
activation of caspase-3 and cleavage of poly ADP-ribose polymerase
(PARP) and lamin A/C, all of which are molecular markers of apoptosis.
These results indicate that inhibition of survival signal ERK1/2, and
subsequent induction of apoptosis, is a critical mechanism of
angiogenesis suppression by EEBP.

Keywords: caspase-3 – human umbilical vein endothelial cells – tube
formation – U0126

For reprints and all correspondence: Toshiro Ohta, Graduate School of
Nutritional and Environmental Sciences, University of Shizuoka, 52-1
Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Tel/Fax:
+81-54-264-5571; E-mail: ohtat@u-shizuoka-ken.ac.jp

*These authors contributed equally to this work.

Current address: Dept. of Food and Nutrition, Dong-A University,
840 Hadan-2 dong, Saha-gu, Busan 604-714, Korea.

Identification of
a bioactive compound isolated from Brazilian propolis type 6

Myrella Lessio Castro^a, Andréa Mendes do Nascimento^b, Masaharu Ikegaki^c, Cláudio M. Costa-Neto^d, Severino M. Alencar^b
and Pedro L. Rosalen^a^,^,

^aDepartment of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), C.P. 52, 13414-903, Piracicaba, SP, Brazil

^bDepartment of Agri-Food Industry, Food and Nutrition, “Luiz de Queiroz” College of Agriculture, University of Sao Paulo (USP), C.P. 9, 13418-900, Piracicaba, SP, Brazil

^cDepartment of Pharmacy, Federal University of Alfenas, Av. Gabriel Monteiro da Silva, 700, 37130-000, Alfenas, MG, Brazil

^dDepartment of Biochemistry and Immunology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (USP), Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil

Received 26 February 2009; revised 28 April 2009; accepted 29 April 2009. Available online 4 May 2009.

Abstract

A prenylated benzophenone, hyperibone A, was isolated from the hexane fraction of Brazilian propolis type 6. Its structure was determined by spectral analysis including 2D NMR. This compound exhibited cytotoxic activity against HeLa tumor cells (IC₅₀ = 0.1756 µM), strong antimicrobial activity (MIC range – 0.73– 6.6 µg/mL; MBC range – 2.92–106 µg/mL) against Streptococcus mutans, Streptococcus sobrinus, Streptococcus oralis, Staphylococcus aureus, and Actinomyces naeslundii, and the results of its cytotoxic and antimicrobial activities were considered good.

Graphical abstract

Keywords: Prenylated benzophenone hyperibone A; Brazilian propolis; Biological activity

http://www.ncbi.nlm.nih.gov/pubmed/18610553
Antivir Chem Chemother. 2008;19(1):7-13.

Anti-influenza virus activity of propolis in vitro and its efficacy
against influenza infection in mice

Shimizu T, Hino A, Tsutsumi A, Park YK, Watanabe W, Kurokawa M.

Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu
University of Health and Welfare, Nobeoka, Miyazaki, Japan.

BACKGROUND: Propolis has been used worldwide as a dietary supplement to
maintain and improve human health. We examined whether ethanol extracts
of Brazilian propolis exhibit antiviral activity against influenza virus
in vitro and in vivo. METHODS: Among 13 ethanol extracts screened in a
plaque reduction assay, four showed anti-influenza virus activity. The
anti-influenza efficacy of the four extracts was further examined in a
murine influenza virus infection model. The mice were infected
intranasally with influenza virus, and the four extracts were orally
administered at 10 mg/kg three times daily for seven successive days
after infection. RESULTS: In this infection model, only one extract,
AF-08, was significantly effective at 10 mg/kg in reducing the body
weight loss of infected mice. The doses of 2 and 10 mg/kg were also
effective in prolonging the survival times of infected mice
significantly, but 0.4 mg/kg was not. The anti-influenza efficacy of
AF-08 at 10 mg/kg was confirmed in a dose-dependent manner in mice.
AF-08 at 10 mg/kg significantly reduced virus yields in the
bronchoalveolar lavage fluids of lungs in infected mice as compared with
the control. The reduction of virus yields by AF-08 at 10 mg/kg
significantly corresponded to those induced by oseltamivir at 1 mg/kg
twice daily from day 1 to day 4 after infection. CONCLUSION: The
Brazilian propolis AF-08 was indicated to possess anti-influenza virus
activity and to ameliorate influenza symptoms in mice. AF-08 may be a
possible candidate for an anti-influenza dietary supplement for humans.

PMID: 18610553 [PubMed - indexed for MEDLINE]

--
Ubi apis ibi salus - Wherever there are bees there is health - Caio Plinio Secondo 23-79 A.D.

Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition

Suresh Awale^a, Feng Li^a, Hiroko Onozuka^b, Hiroyasu Esumi^b, Yasuhiro Tezuka^a and Shigetoshi Kadota^a^,

^aInstitute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
^bInvestigative Treatment Division, National Cancer Center Research Institute East, Chiba 277-8577, Japan

Received 27 August 2007; revised 18 September 2007; accepted 2 October 2007. Available online 5 October 2007.

Abstract

Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticancer drug development. In this study, the MeOH soluble extract of Brazilian red propolis was found to kill 100% PANC-1 cells preferentially in the nutrient-deprived condition at the concentration of 10 µg/mL. Further phytochemical investigation led to the isolation of 43 compounds including three new compounds, (6aS,11aS)-6a-ethoxymedicarpan (1), 2-(2',4'-dihydroxyphenyl)-3-methyl-6-methoxybenzofuran (2), and 2,6-dihydroxy-2-[(4-hydroxyphenyl)methyl]-3-benzofuranone (3). Among them, (6aR,11aR)-3,8-dihydroxy-9-methoxypterocarpan (21, DMPC) displayed the most potent 100% preferential cytotoxicity (PC₁₀₀) at the concentration of 12.5 µM. Further study on the mode of cell death induced by DMPC against PANC-1 cells indicated that killing process was not accompanied by DNA fragmentation, rather through a nonapoptotic pathway accompanied by necrotic-type morphological changes.

Graphical abstract

Keywords: Pancreatic cancer; PANC-1; Anti-austerity; Screening strategy; Red propolis; 3,8-Dihydroxy-9-methoxypterocarpan; Anti-cancer agent

Article in Press, Corrected Proof

In vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp-2) Cells
Michelle C. Búfalo, João M. G. Candeias and José Maurício Sforcin

Department of Microbiology and Immunology, Biosciences Institute, UNESP, 18618-000 Botucatu, S.P., Brazil

Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2) cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better
comprehension of propolis's antitumor action.

Keywords: antitumor action – HEp-2 cells – propolis

© 2007 The Author(s).
This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits
unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.

Propolis May Prevent Growth of Tumor Blood Vessels

Researchers at University of Shizuoka Target Angiogenesis
Oncology Business Week, September 30, 2007

"Propolis, a resinous substance collected by honeybees from various plant sources, possesses various physiological activities such as antitumor effects. We have previously shown that propolis of Brazilian origin was composed mainly of artepillin C and that its constituents were quite different from those of propolis of European origin," scientists writing in the journal Cancer Letters report.

"In this report, we examined an was responsible for such effects. In an in propolis and investigated whether artepillin C antiangiogenic effects of Brazilian vivo angiogenesis assay using ICR mice, we found that the ethanol extract of Brazilian propolis (EEBP) significantly reduced the number of newly formed vessels. EEBP also showed antiangiogenic effects in an in vitro tube formation assay. When compared with other constituents of EEBP, only artepillin C was found to significantly inhibit the tube formation of HUVECs in a concentration-dependent manner (3.13-50 mu g/ml). In addition, artepillin C significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-50 mu g/ml). Furthermore, artepillin C significantly reduced the number of newly formed vessels in an in vivo angiogenesis assay. Judging from its antiangiogenic activity in vitro and in vivo, we concluded that artepillin C at least in part is responsible for the antiangiogenic activity of EEBP in vivo," wrote M.R. Ahn and colleagues, University of Shizuoka.

The researchers concluded: "Artepillin C may prove useful in the development of agents and foods with therapeutic or preventive activity against tumor angiogenesis."…

Int J Oncol. 2007 Sep;31(3):601-6.

Antiproliferation of human prostate cancer cells by ethanolic extracts
of Brazilian propolis and its botanical origin.

Li H, Kapur A, Yang JX, Srivastava S, McLeod DG, Paredes-Guzman JF, Daugsch A, Park YK, Rhim JS.

Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Propolis is a resinous substance collected by bees (Apis mellifera) from various tree buds which they then use to coat hive parts and to seal cracks and crevices in the hive. Propolis, a known ancient folk medicine, has been extensively used in diet to improve health and to prevent disease. In the present study, we have evaluated the effects of ethanolic extracts of Brazilian propolis group l2 and bud resins of botanical origin (B. dracunculifolia), and propolis group 3 on proliferation of metastasis (DU145 and PC-3) and primary malignant tumor (RC58T/h/SA#4)-derived human prostate cancer cells. The strongest inhibition was observed in propolis group 3 (sample #3) extracts whereas moderate growth inhibition was observed in human prostate epithelial cells. In the RC58T/h/SA#4 cells, resins of botanical origin of propolis group 12 (sample #1) and propolis group 12 (sample #2) induced growth inhibition that was associated with S phase arrest whereas propolis group 3 (sample #3) induced growth inhibition that was associated with G2 arrest. The mechanisms of cell cycle effects of propolis were
investigated. The resins of botanical origin of propolis group 12 and propolis group 12 showed similar inhibition of cyclin D1, CDK4 and cyclin B1 expression. Propolis group 3 showed higher induction of p21 expression but no inhibition of cyclin D1, CDK4 and cyclin B1 expression. The results obtained here demonstrate that the Brazilian propolis extracts have significant inhibitory effect on proliferation of human prostate cancer cells. Inhibition was achieved through regulation of protein expression of cyclin D1, B1 and cyclin dependent kinase (CDK) as well as p21. Our results indicate that the Brazilian propolis extracts show promise as chemotherapeutic agents as well as preventive agents against prostate cancer.

PMID: 17671687 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17671687

Suppression of tumor-induced angiogenesis by Brazilian propolis: Major component Artepillin C inhibits in vitro tube formation and endothelial cell proliferation.

Propolis, a resinous substance collected by honeybees from various plant sources, possesses various physiological activities such as antitumor effects. We have previously shown that propolis of Brazilian origin was composed mainly of artepillin C and that its constituents were quite different from those of propolis of European origin. In this report, we examined an antiangiogenic effects of Brazilian propolis and investigated whether artepillin C was responsible for such effects. In an in vivo angiogenesis assay using ICR mice, we found that the ethanol extract of Brazilian propolis (EEBP) significantly reduced the number of newly formed vessels. EEBP also showed antiangiogenic effects in an in vitro tube formation assay. When compared with other constituents of EEBP, only artepillin C was found to significantly inhibit the tube formation of HUVECs in a concentration-dependent manner (3.13-50mug/ml). In addition, artepillin C significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-50mug/ml). Furthermore, artepillin C significantly reduced the number of newly formed vessels in an in vivo angiogenesis assay. Judging from its antiangiogenic activity in vitro and in vivo, we concluded that artepillin C at least in part is responsible for the antiangiogenic activity of EEBP in vivo. Artepillin C may prove useful in the development of agents and foods with therapeutic or preventive activity against tumor angiogenesis.

Keywords: artepillin, propolis, significantly, antiangiogenic, effects, activity, assay, angiogenesis, brazilian, tube formation, concentration dependent, dependent manner, antiangiogenic activity, formed vessels, newly formed, brazilian propolis, vivo angiogenesis, angiogenesis assay, significantly reduced, antiangiogenic effects

Authored by Ahn MR, Kunimasa K, Ohta T, Kumazawa S, Kamihira M, Kaji K,
Uto Y, Hori H, Nagasawa H, Nakayama T. Laboratory of Functional Food
Science and COE Program in the 21st Century, School of Food and
Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
Shizuoka 422-8526, Japan.

Published in Cancer Lett. 2007 Jul 18;252(2):235-43. Epub 2007 Mar 6.

Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis.

Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection ( I. P.) of G1 inhibited acetic acid-induced abdominal constrictions with an ID (50) = 0.75 +/- 0.05 mg/kg, and in the formalin test the ID (50) values were 0.85 +/- 0.07 mg/kg and 13.88 +/- 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered I. P. and of 36 % after 15 min by the oral route ( O. R.). When the inflammatory agent was complete Freund's adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID (50) values were 1.09 +/- 0.08 mg/kg ( I. P.) and 10.00 +/- 0.90 mg/kg ( O. R.). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC (50) values of 0.72 +/- 0.08 mg/kg and 4.17 +/- 0.50 mg/kg, by I. P. or O. R. administration, with a preferential migration of polymorphonuclear neutrophils. IN VITRO, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC (50) = 41.60 microg/mL), and also the luciferase activity in TNF-alpha-stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-kappaB sites in the iNOS promoter.

Publication Types: Research Support, Non-U.S. Gov't

Keywords: induced, inflammatory, kappab, extract, inhibition, edema, values, anti inflammatory, values were, mouse models

Authored by Paulino N, Teixeira C, Martins R, Scremin A, Dirsch VM,
Vollmar AM, Abreu SR, de Castro SL, Marcucci MC. Grupo de Pesquisa e
Desenvolvimento de Biofarmacos BIOFAR, Universidade do Sul de Santa
Catarina, Tubarao/SC, Brazil. niraldo@unisul.br

Published in Planta Med. 2006 Aug;72(10):899-906. Epub 2006 Aug 10.

Potent free radical scavenging activity of propol isolated from Brazilian propolis.

We evaluated free radical scavenging activity of the water, methanol and chloroform extracts of propolis in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and xanthine-xanthine oxidase (XOD) generated superoxide anion assay systems. The free radical scavenging activity guided fractionation and chemical analysis led to the isolation of a new compound, propol (3-[4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl]-acrylic acid) from the water extract, which was more potent than most common antioxidants such as vitamin C and vitamin E (alpha-tocopherol) in these assay systems.

Keywords: radical, free radical, assay systems, radical scavenging, scavenging activity

Authored by Basnet P, Matsuno T, Neidlein R. Pharmazeutisch-Chemisches
Institut, Universitat Heidelberg, Germany.

Published in Z Naturforsch [C]. 1997 Nov-Dec;52(11-12):828-33.

Resveratrol and propolis extract: an insight into the morphological and molecular changes induced in DU145 cells.

In the Western world cancer is the second leading cause of mortality, and prostate carcinoma represents in men the second most important type of cancer-causing death. We have already shown that resveratrol (200 microM) triggers in DU145, an androgen-resistant prostate cancer cell line, a necrotic-like cell death, while propolis ethanolic extract (100 microg/ml) causes an apoptotic-like cell demise. The present research is aimed to better elucidate the molecular mechanisms activated by the two micronutrients. Vinorelbine bitartrate, a drug widely used in prostate cancer therapy, was utilized as a reference drug, because it is known to induce apoptosis. The combined treatments between the micronutrients and vinorelbine have been studied to test a possible vinorelbine dose reduction, avoiding its side effects without altering its cytotoxic action. In this investigation SEM and TEM analyses were performed to examine the morphological modifications induced; our observations confirmed necrotic cell features after treatment with resveratrol, and apoptotic modifications after propolis. We also measured cell cycle progression to study a correlation with p21 and p53, two well-known cell cycle checkpoints. The levels of HSP27 and HSP70, two chaperones also exerting antioxidant/antiapoptotic functions, were been also analyzed. Our data indicate that the two micronutrients modulate cell cycle distribution, increasing p53 levels, without the induced HSPs being able to rescue DU145 from death. The results presented suggest chemotherapy based on resveratrol and propolis, alone or in combination with vinorelbine, as a potential useful tool for prostate cancer therapy; the increase in cell cycle control and the modulation of HSPs expression reinforce this suggestion.

Publication Types: Comparative Study,

Research Support, Non-U.S. Gov't

Keywords: cancer, vinorelbine, cycle, prostate, micronutrients, resveratrol, death, propolis, cell cycle, prostate cancer, like cell, cancer therapy

Authored by Scifo C, Milasi A, Guarnera A, Sinatra F, Renis M.
Dipartimento di Chimica Biologica, Chimica Medica e Biologia Molecolare,
Universita di Catania, Italy.

Published in Oncol Res. 2006;15(9):409-21.

Identification of caffeoylquinic acid derivatives from Brazilian propolis as constituents involved in induction of granulocytic differentiation of HL-60 cells.

We have previously reported that Brazilian propolis extracts inhibited growth of HL-60 human myeloid leukemia cells, which is partly attributed to the induction of apoptosis associated with granulocytic differentiation.

In this study, we isolated three compounds which induce granulocytic differentiation evaluated by nitroblue tetrazolium (NBT)-reducing assays from the water extract of propolis and identified as 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic, and 3,4-di-O-caffeoylquinic acids by NMR analysis. Cell growth inhibitory activity of these caffeoylquinic acids was found in HL-60 cell, which was mainly attributed to the induction of apoptosis. Furthermore, the
potency of caffeoylquinic acid derivatives to induce granulocytic differentiation was examined in HL-60 cells. Caffeic, quinic, and chlorogenic acids had no effects on the NBT-reducing activity, while 3,4,5-tri-O-caffeoylquinic acid induced more than 30% of NBT-positive cells. These results suggest that the number of the caffeoyl groups bound to quinic acid plays an important role in the potency of the caffeoylquinic acid derivatives to induce granulocytic differentiation. This is the first report demonstrating that the caffeoylquinic acid derivatives induce granulocytic differentiation of HL-60 cells.

Keywords: caffeoylquinic, differentiation, granulocytic, induce, cells, derivatives, acids, granulocytic differentiation, caffeoylquinic acid, induce granulocytic, acid derivatives, caffeoylquinic acids

Authored by Mishima S, Inoh Y, Narita Y, Ohta S, Sakamoto T, Araki Y,
Suzuki KM, Akao Y, Nozawa Y. Nagaragawa Research Center, API Co., Ltd.,
692-3 Nagara, Gifu 502-0071, Japan.

Published in Bioorg Med Chem. 2005 Oct 15;13(20):5814-8.

Radioprotective effects of propolis to the teratogenic effects of the mice in radiation.

http://sciencelinks.jp/j-east/article/200224/000020022402A0788425.php
Research Reports of Suzuka University of Medical Science(2002)
Accession number 02A0788425
Author: GU Y(Suzuka Univ. Medical Sci.)   HASEGAWA T(Suzuka Univ.
Medical Sci.)   SUZUKI I(Suzuka Univ. Medical Sci.)   PARK S(Suzuka
Univ. Medical Sci.)   OSHIMA M(Suzuka Univ. Medical Sci.)   TAKAGI
Y(Suzuka Univ. Medical Sci.)   IWASA M(Suzuka Univ. Medical Sci.)   MORI
T(Suzuka Univ. Medical Sci.)   BAMEN K(Bio Queen Co., Ltd.)

Journal Title: Research Reports of Suzuka University of Medical Science
Journal Code: L2873A ISSN:1348-0227 VOL. NO.9 PAGE.15-33(2002)
Figure&Table&Reference: FIG.7, TBL.3, REF.61
Pub. Country: Japan Language: English

Identification of caffeoylquinic acid derivatives from Brazilian propolis as constituents involved in induction of granulocytic differentiation of HL-60 cells.

* Mishima S, * Inoh Y, * Narita Y, * Ohta S, * Sakamoto T, * Araki Y, * Suzuki KM, * Akao Y, * Nozawa Y.
Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Gifu 502-0071, Japan.

We have previously reported that Brazilian propolis extracts inhibited growth of HL-60 human myeloid leukemia cells, which is partly attributed to the induction of apoptosis associated with granulocytic differentiation. In this study, we isolated three compounds which induce granulocytic differentiation evaluated by nitroblue tetrazolium (NBT)-reducing assays from the water extract of propolis and identified as 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic, and 3,4-di-O-caffeoylquinic acids by NMR analysis. Cell growth inhibitory activity of these caffeoylquinic acids was found in HL-60 cell, which was mainly attributed to the induction of apoptosis. Furthermore, the potency of caffeoylquinic acid derivatives to induce granulocytic differentiation was examined in HL-60 cells. Caffeic, quinic, and chlorogenic acids had no effects on the NBT-reducing activity, while 3,4,5-tri-O-caffeoylquinic acid induced more than 30% of NBT-positive cells. These results suggest that the number of the caffeoyl groups bound to quinic acid plays an important role in the potency of the caffeoylquinic acid derivatives to induce granulocytic differentiation. This is the first report demonstrating that the caffeoylquinic acid derivatives induce granulocytic differentiation of HL-60 cells.

PMID: 15993085 [PubMed - indexed for MEDLINE]

Biol Pharm Bull. 2004 May;27(5):727-30.Click here to read

Inhibitory effect of Propolis on the growth of Human Leukemia U937.

* Aso K, * Kanno S, * Tadano T, * Satoh S, * Ishikawa M.
Department of Pharmacology and Toxicology, Cancer Research Institute,
Tohoku Pharmaceutical University, Sendai, Japan.

We have investigated the effect of propolis (CB Propolis) on the growth of human histiocytic lymphoma U937 cells. We found that propolis strongly inhibited the growth of the cells and macromolecular synthesis in a dose- and time-dependent manner by apoptosis. Propolis at 0.015-0.5 microl/ml showed antitumor activity with an IC(50) of 0.18 microl/ml for 3 d. It also inhibits DNA, RNA and protein synthesis with an IC(50) of 0.08, 0.17 and 4.3 microl/ml, respectively. The inhibitory effect on DNA synthesis was partially irreversible. Moreover, an apoptotic DNA ladder and chromatin condensation were observed in the same concentration range in which cell growth was inhibited. The caspase inhibitor, Z-Asp-CH(2)-DCB, prevented DNA fragmentation. These results suggest that the antitumor activity of propolis occurs through the induction of apoptosis. Propolis may be useful as a cancer chemopreventive and chemotherapeutic agent.

PMID: 15133255 [PubMed - indexed for MEDLINE]

Nutrition and Cancer
2003, Vol. 47, No. 2, Pages 156-163
(doi:10.1207/s15327914nc4702_8)

Inhibitory Effect of Water-Soluble Derivative of Propolis and Its Polyphenolic Compounds on Tumor Growth and Metastasizing Ability: A Possible Mode of Antitumor Action

Nada Orsolic ??Lidija Sver ??Svjetlana Terzic ??Zoran Tadic ??Ivan Basic ??

Abstract

Polyphenolic compounds are widely distributed in the plant kingdom and display a variety of biological activities, including chemoprevention and tumor growth inhibition. Propolis is made up of a variety of polyphenolic compounds. We compared how the routes of administration of polyphenolic compounds deriving from propolis and of propolis itself affect the growth and metastatic potential of a transplantable mammary carcinoma (MCa) of the CBA mouse. The influence of tested compounds on local tumor growth was also studied. Metastases in the lung were generated by 2 105 tumor cells injected intravenously (IV). A water-soluble derivative of propolis (WSDP) and polyphenolic compounds (caffeic acid, CA, and CA phenethyl ester, CAPE) were given to mice per os (PO) or intraperitoneally (IP) before or after tumor cell inoculation. Tested compounds significantly decreased the number of lung colonies. When mice were inoculated with 105 MCa cells in the exact site of subcutaneous injection of different doses of WSDP, CA, or CAPE, tumor growth was inhibited, and survival of treated mice was prolonged. Antitumor activity, according to the results obtained, is mostly related to the immunomodulatory properties of the compounds and their capacity to induce apoptosis and necrosis. In conclusion, results presented here indicate that WSDP, CA, and CAPE could be potential useful tools in the control of tumor growth in experimental tumor models when administrated PO; because PO administration is the easiest way of introducing a compound used for prevention and/or cure of any disease, it is likely that this article has reached the goal of the investigation.

Cited by
Nada Or??n>, Svjetlana Terzi?an>, Lidija ?/span>, Ivan Ba?/span>??. (2005) Honey-bee products in prevention and/or therapy of murine transplantable tumours. Journal of the Science of Food and Agriculture 85:3, 363
CrossRef
Nada Oršolić, Ivan Kosalec, Ivan Bašić??. (2005) Synergystic Antitumor Effect of Polyphenolic Components of Water Soluble Derivative of Propolis against Ehrlich Ascites Tumour. Biological & Pharmaceutical Bulletin 28:4, 694
CrossRef
N. Or?, S. Terzic, L. ?/span>, I. Ba?span>??. (2005) Polyphenolic compounds from propolis modulate immune responses and increase host resistance to tumour cells. Food and Agricultural Immunology 16:3, 165
CrossRef

National Cancer Institute

A benzo-gamma-pyran derivative isolated from Propolis, inhibits growth of MCF-7 Human Breast Cancer cells.

3 UI - 21388205 AU - Luo J; Soh JW; Xing WQ; Mao Y; Matsuno T; Weinstein IB TI - PM-3,

SO - Anticancer Res 2001 May-Jun;21(3B):1665-71 AD

Herbert Irving Comprehensive Cancer Center, Columbia Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. AB -

Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. Several components isolated from propolis have been shown to have anticancer activity. This study demonstrates that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity.
Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.

http://cancerweb.ncl.ac.uk/cancernet/cancerlit/709010.html

PMID: 11299738 [PubMed - indexed for MEDLINE]

Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis.

* Kimoto T, * Aga M, * Hino K, * Koya-Miyata S, * Yamamoto Y, * Micallef MJ, * Hanaya T, * Arai S, * Ikeda M, * Kurimoto M.
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Fujisaki 675-1, Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp

Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of Brazilian propolis that possesses anti-tumor activity. When Artepillin C was applied to human leukemia cell lines of different phenotypes, namely, lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C exhibited potent cytocidal effects and induced marked levels of apoptosis in all the cell
lines. The most potent effects were observed in the T-cell lines. Apoptotic bodies and DNA fragmentation were induced in the cell lines after exposure to Artepillin C. DNA synthesis in the leukemia cells was clearly inhibited and disintegration of the cells was confirmed microscopically. Apoptosis of the leukemia cells may be partially associated with enhanced Fas antigen expression and loss of mitochondrial membrane potential. In contrast, although Artepillin C inhibited the growth of pokeweed mitogen (PWM)-stimulated normal blood lymphocytes, it was not cytocidal to normal unstimulated lymphocytes. These results suggested that Artepillin C, an active ingredient of Brazilian propolis, has anti-leukemic effects with limited inhibitory effects on normal lymphocytes.

Ethnopharmacol. 2005 May 13;99(1):5-11.Click here to read Links

Effects of propolis on cell growth and gene expression in HL-60 cells.

* Mishima S, * Narita Y, * Chikamatsu S, * Inoh Y, * Ohta S, * Yoshida C, * Araki Y, * Akao Y, * Suzuki KM, * Nozawa Y.
Nagaragawa Research Center, API Co. Ltd., 692-3 Nagara, Gifu 502-0071, Japan.

Brazilian propolis obtained from honeybee hives was extracted with water or ethanol. Cell growth-inhibitory activities of these propolis extracts were found in HL-60 human myeloid leukemia cells. The extracts-induced apoptosis in the cells, which was characterized by morphological and nucleosomal DNA fragmentation analysis. The apoptosis was mainly attributed to the induction of granulocytic differentiation, which was evaluated by nitro blue tetrazolium (NBT) reducing assays and cytofluorometric analysis for the expression of cell surface marker CD11b. DNA microarray analysis was performed to examine the gene expression profiles in the propolis-treated HL-60 cells accompanied with granulocytic differentiation, which were compared with those in all-trans retinoic acid-treated cells. Several genes were up- or down-regulated. Two genes encoding S100 calcium binding protein A9 and ferritin, heavy polypeptide 1 were up-regulated, which were also confirmed by semi-quantitative reverse transcriptase-PCR (RT-PCR). Propolis-induced growth inhibition in HL-60 cells was, at least in part, due to differentiation with gene expression profiles, which are similar to those induced by all-trans retinoic acid.

PMID: 15848013 [PubMed - indexed for MEDLINE]

International Journal of Cancer Research 3 (1): 43-53, 2007

Biological Therapy Using Propolis as Nutritional Supplement in Cancer Treatment

J. Galvao, J.A. Abreu, T. Cruz, G.A.S. Machado, P. Niraldo, A. Daugsch, C.S. Moraes, P. Fort and Y.K. Park F

Abstract: Neoplasia cause several disorders in the affected body, such as suppression of immune function besides emotional and social impairments. Therefore, handling patients can be extremely difficult, offering several challenges in choosing the appropriate treatment option to be used. The right selection of treatment demands special attention. Chemotherapy is usually the standard treatment, although there are many other different therapeutic modalities also used in medicine. The present study is a literature review focusing on the pharmacological properties of propolis, the resinous product collected by the honeybee from different plant sources, which represents a secure and efficient option for biological therapy and cancer prevention.

Downloadable from: http://198.170.104.138/ijcr/0/91-IJCR.pdf

The American Journal of Chinese Medicine, Vol. 33, No. 2, 231–240
© 2005 World Scientific Publishing Company Institute for Advanced Research in Asian Science and Medicine

Immune Activation and Radioprotection by Propolis

Yasuyuki Takagi, In-Sook Choi, Takenori Yamashita, Takashi Nakamura, Ikukatsu Suzuki, Takeo Hasegawa, Masami Oshima and Yeun-Hwa Gu
Graduate School of Health Science, Suzuka University of Medical Science
1001-1 Kishioka-cho, Suzuka-shi, Mie 510-0293, Japan
Research in Asian Science and Medicine

Abstract:

In this study, we focused on immune stimulation by Propolis, and examined changes in the effect of irradiation after Propolis administration. We also examined the radioprotective effect of Propolis by observing its effect on the immune system. The effect of immune activation by Propolis was investigated by measuring the total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune activation by Propolis was investigated by measuring the T-lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Compared with the control group, the IgG was significantly reduced in the Propolis group, indicating that Propolis suppressed IgG production. ELISA revealed that the amount of IgM in mouse serum was significantly higher in the Propolis group as compared with the control group, indicating that Propolis increased IgM production. The number of CD4-positive cells was increased only in the Propolis group. Likewise, the number of CD4-positive cells increased by 81% in the Propolis with irradiation group compared with the irradiation group alone. Compared with the control group, the Propolis group increased CD8-positive cells. Compared with the irradiation alone group, CD8-positive cells were decreased by Propolis with irradiation group. Propolis activated macrophages to stimulate interferon (IFN)-? production in association with the secondary activation of T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate. In addition, activated macrophages in association with the secondary T-lymphocyte activation increased IFN-? production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.
Keywords: Propolis; Radiation Protection; T-Lymphocyte; IgG; IgM; CD4; CD8.

Research in Asian Science and MedicineResearch in Asian Science and Medicine
Correspondence to: Dr. Yeun-Hwa Gu, Graduate School of Health Science,
Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka-shi,
Mie 510-0293, Japan. Tel: (+81) 593-83-8991, Fax: (+81) 593-83-9666,
E-mail: gu@suzuka-u.ac.jp

Antioxidant activity and anti-tumor immunity by Agaricus, Propolis and Paffia in mice
Yeun-hwa Gu, Graduate School of Health Science, Suzuka University of Medical Science
Key Words: Antioxidant activity, Anti-tumor immunity, Agaricus, Propolis, Paffia

Abstract:

Various previously intractable diseases have been overcome by the development of many new medicines. However, cancer is still a major cause of death. In the process of carcinogenesis, a multistep accumulation of gene mutations causes malignant transformation, and the probability of gene mutations is different depending on genetic and environmental factors. Individual differences are found in the susceptibility to cancer, and prevention of carcinogenesis is possible. In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Agaricus, Propolis and Paffia, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. When the antioxidant activities of Agaricus, Propolis and Paffia were examined by the DPPH and Rhoudan iron methods, since Propolis contains high levels of fravonoids, it is thought that fravonoids may be responsible for the antioxidant activity in this study. In the examination of immunoenhancement activity, we measured lymphocyte versus polymorophonuclear leukocyte ratios (L/P activity). The number of lymphocytes was significantly increased in groups treated with Proplolis. Specifically, slightly high levels of IFN-g were measured in mice bearing the S-180
carcinoma, after administration of Agaricus, Propolis and Paffia. This strongly suggests that cellular immunity is especially activated by treatment with Agaricus, Propolis and Paffia, because production of IFN-g is limited to the T cells and NK cells stimulated by mitogen and sensitized antigen. TNF-a shows a different extent and mechanism of action depending on the target cells. When TNF-a was measured in mice bearing the S-180 carcinoma, mice treated with Agaricus, Propolis and Paffia showed slightly higher TNF-a levels as compared to the control group. This suggests that activated macrophages produce TNF-a in mice treated with Agaricus, Propolis and Paffia, since activated macrophages and lymphocytes are the source of most TNF-a. When anti-tumor action was examined using two kinds of sarcoma (Sarcoma-180 carcinoma), tumor-suppressive ratios after treatment with Propolis was 29.1%. When Sarcoma-180 solid carcinoma was used, tumor-suppressive ratios were 62%. Thus, Propolis showed strong anti-tumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that Agaricus, Propolis and Paffia enhances original functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

Antioxidative bioavailability of Artepillin C in Brazilian propolis

Kazuo Shimizu,a Hitoshi Ashida,a Yukinaga Matsuura,b and Kazuki Kanazawaa,*
a Department of Life Science, Graduate School of Science and Technology,
Kobe University, Rokkodai, Nada-ku, Kobe 657-8501, Japan
b Yamada Apiculture Center, Inc.,
194 Ichiba, Kagamino, Tomata-gun,
Okayama 708-0393, Japan
Received 18 December 2003, and in revised form 28 January 2004 Elsevier Inc.

Abstract:

Propolis has strong antioxidative activity. We investigated here whether this activity was available in intestinal Caco-2 and hepatic HepG2 cells. Phenolics in Brazilian propolis, extracted with ethyl acetate after the removal of resin and wax with 90% methanol, included artepillin C at 21 mmol/100 g, p-coumaric acid and cinnamic acid relatives 24 mmol, kaempferol and its derivatives 9.4 mmol, naringenin 2.8 mmol, isosakuranetin 0.9 mmol, chrysin at 0.8 mmol/100 g, and several minor components. When the extract was added to the apical side of Caco-2 monolayers, artepillin C was specifically incorporated into the cells and released to the basolateral side mostly without conjugation. Then, artepillin C was added to HepG2 cells and exposed to reactive oxygens. Artepillin C prevented oxidative damage dose-dependently, and suppressed lipid peroxidation evaluated with thiobarbituric acid reactive substances by 16% and the formation of 8-hydroxy-20-deoxyguanosine in DNA by 36% at a concentration of 20 uM. Artepillin C is a bioavailable antioxidant.

Keywords: Propolis; Polyphenols; Artepillin C; Antioxidant; Bioavailability; 8-OHdG; Caco-2; HepG2

MOLECULAR CARCINOGENESIS 44:293–299 (2005) Wiley-Liss, Inc.

Artepillin C in Brazilian Propolis Induces G0/G1 Arrest via Stimulation
of Cip1/p21 Expression in Human Colon Cancer Cells

Kazuo Shimizu,1 Swadesh K. Das,1 Takashi Hashimoto,1 Yoshihiro Sowa,2 Tatsushi Yoshida,2 Toshiyuki Sakai,2 Yukinaga Matsuura,2 and Kazuki Kanazawa 1*
1Department of Life Science, Graduate School of Science and Technology,
Kobe University, Kobe, Japan
2Department of Molecular-Targeting Cancer Prevention, Graduate School of
Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
3Yamada Apiculture Center, Inc., Okayama, Japan

Abstract:

Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G0/G1 arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G0/G1 arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.

Key words: propolis; artepillin C; colon cancer; cell-cycle arrest; Cip1/p21

Journal of Pharmacy and Pharmacology

Baccharis dracunculifolia, the main botanical source of Brazilian green propolis, displays antiulcer activity

Marivane Lemos, Muriel Primon de Barros, João Paulo Barreto Sousa, Ademar Alves da Silva Filho, Jairo Kenupp Bastos and Sérgio Faloni de Andrade

Núcleo de Ciência e Tecnologia, Área de Ciências Biológicas e da Saúde,
Universidade do Oeste de Santa Catarina, Campus de Videira, Rua Paese,
198, Bairro das Torres, Videira-SC, 89560-000, SC, Brazil

Abstract:

Baccharis dracunculifolia is the most important botanical source of Southeastern Brazilian propolis, known as green propolis for its colour. In a previous study, we described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. We therefore wanted to investigate the possibility of using B. dracunculifolia extract for antiulcer treatment. This study was undertaken to evaluate the anti-ulcerogenic property of hydroalcoholic extract of B. dracunculifolia aerial parts. The HPLC analysis of the chemical composition of B. dracunculifolia extract used in this study revealed the presence mainly of cinnamic acid derivates and flavonoids. Doses of 50, 250 and 500 mg/kg of B. dracunculifolia crude extract and positive controls (omeprazole or cimetidine) significantly diminished the lesion index, the total lesion area and the percentage of lesion compared with negative control groups. The percentage of ulcer inhibition was significantly higher in groups treated with B. dracunculifolia, cimetidine or omeprazole, with all protocols used, compared with negative control groups. Regarding the model of gastric secretion, reductions in the volume of gastric juice and total acidity were observed, as well as an increase in the gastric pH. These results were
similar to results from studies carried out with green propolis extract. Although more investigations are required, our results suggest that B. dracunculifolia has potential to be used as a phytotherapic preparation for the treatment of gastric ulcer.

Evaluation of the Analgesic and Anti-Inflammatory Effects of a Brazilian Green Propolis

DOI: 10.1055/s-2006-947185
Niraldo Paulino1, Cristiane Teixeira1, Regiane Martins1, Amarilis Scremin1, Verena M. Dirsch2, Angelika M. Vollmar2, Sheila R. L. Abreu3, Solange L. de Castro4, Maria Cristina Marcucci5
1 Grupo de Pesquisa e Desenvolvimento de Biofármacos (BIOFAR),
Universidade do Sul de Santa Catarina, Tubarão/SC, Brazil
2 Institute of Pharmacy, University of Munich, Munich, Germany
3 Nectar Pharmaceuticals, Belo Horizonte, Minas Gerais, Brazil
4 Departamento de Ultra-estrutura e Biologia Celular, IOC, Fundação
Oswaldo Cruz, Rio de Janeiro, Brazil
5 Faculdade de Farmácia, Departamento de Pesquisa e Extensão,
Universidade Bandeirante de São Paulo, São Paulo, Brazil
Original Paper Pharmacology Planta Med 2006; 72: 899-906

Abstract:

Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection (i. p.) of G1 inhibited acetic acid-induced abdominal constrictions with an ID50 = 0.75 ± 0.05 mg/kg, and in the formalin test the ID50 values were 0.85 ± 0.07 mg/kg and 13.88 ± 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered i. p. and of 36 % after 15 min by the oral route (o. r.). When the inflammatory agent was complete Freund’s adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID50 values were 1.09 ± 0.08 mg/kg (i. p.) and 10.00 ± 0.90 mg/kg (o. r.). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC50 values of 0.72 ± 0.08 mg/kg and 4.17 ± 0.50 mg/kg, by i. p. or o. r. administration, with a preferential migration of polymorphonuclear neutrophils. In vitro, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC50 = 41.60 µg/mL), and also the luciferase activity in TNF-a-stimulated HEK 293 cells transfected with NF-?B-luciferase reporter gene driven by the nuclear factor ?B (NF-?B) (IC50 = 200 µg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-?B sites in the iNOS promoter. Abbreviations CFA:complete Freund adjuvant COX-2:inducible isoform of cyclooxygenase Indo:Indomethacin iNOS:inducible nitric oxide synthase LPS:Lipopolysaccharide MI:maximal inhibition MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide NF-?B:nuclear factor ?B NO:nitric oxide TMB:3,3',5,5'-tetramethylbenzidine

Key words Typified propolis - analgesic effect - anti-inflammatory effect - NF-?B factor - nitric oxide

Immunomodulation produced by a green propolis extract on humoral and
cellular responses of mice immunized with SuHV-1
Vaccine 25 (2007) 1250–1256 Elsevier
Geferson Fischer a,b,*, Fabricio Rochedo Conceicao a,b, Fabio Pereira Leivas Leite a,c,Luana Alves Dummera,b, Gilberto D’Avila Vargas b, Silvia de Oliveira Hubner b,Odir Antonio Dellagostin a,c, Niraldo Paulino d, Amarilis Scremin Paulino d, Telmo Vidor b

a Centro de Biotecnologia, Universidade Federal de Pelotas (UFPel), CP
354, 96010-900 Pelotas, RS, Brazil
b Laboratorio de Virologia e Imunologia, Faculdade de Veterinaria,
UFPel, CP 354, 96010-900 Pelotas, RS, Brazil
c Instituto de Biologia, UFPel, CP 354, 96010-900 Pelotas, RS, Brazil
d Curso de Farmacia, Universidade Barriga Verde, UNIBAVE, Rua Miguel
Couto 330, 88870-000 Orleans, SC, Brazil
Received 4 September 2006; received in revised form 4 October 2006;
accepted 4 October 2006
Available online 18 October 2006

Abstract:

Despite recent technological advances in vaccine production, most the vaccines depend on the association with adjuvant substances. This work evaluated the adjuvant capacity of an ethanol extract of green propolis associated to inactivated Suid herpesvirus type 1 (SuHV-1) vaccine preparations. Mice inoculated with SuHV-1 vaccine plus aluminum hydroxide and 5 mg/dose of propolis extract presented higherlevels of antibodies when compared to animals that received the same vaccine without propolis. The use of SuHV-1 vaccine with propolis extract alone did not induce significant levels of antibodies, however it was able to increase the cellular immune response, evidenced by the increase in the expression of mRNA to IFN-gamma. Besides, propolis increased the percentage of protected animals against challenge with a lethal dose of SuHV-1. The effect of green propolis extract on the humoral and cellular immune responses may be exploited for the development of effective vaccines.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Green propolis; Adjuvant; Vaccines

J Ethnopharmacol. 2006 Oct 28

Effect of Brazilian green propolis on experimental gastric ulcers in rats.

de Barros MP, Sousa JP, Bastos JK, de Andrade SF

Nucleo de Ciencia e Tecnologia, Area de Ciencias Biologicas e da Saude, Universidade do Oeste de Santa Catarina, Campus de Videira, SC, Brazil.

Propolis is a resinous hive product collected by honeybees from plants. The propolis produced in Southeastern of Brazil is known as green propolis because of its color. Modern herbalists recommend its use because it displays antibacterial, antifungal, antiviral, hepatoprotective, anti-inflammatory, immunomodulatory and anti-ulcer properties. The anti-ulcer activity of green propolis hydroalcoholic crude extract was evaluated by using models of acute gastric lesions induced by ethanol, indomethacin and stress in rats. Moreover, the effects of extract on gastric content volume, pH and total acidity, using pylorus ligated model were evaluated. Animals pretreated with propolis hydroalcoholic crude extract (50, 250 and 500mg/kg) showed a significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (p<0.05) in the ethanol-induced ulcer model. Green propolis extract, at a higher dose (500mg/kg), displayed a significant protection by reducing (p<0.05) the evaluated parameters in the gastric ulceration induced by indomethacin. In the stress-induced ulcer model it was observed a significant reduction (p<0.05) in those parameters in animals treated with green propolis extract (250 and 500mg/kg). Regarding the pylorus ligated model it was observed that green propolis extract (250 and 500mg/kg) displayed an anti-secretory activity, which lead to a reduction in the gastric juice volume, total acidity and pH. These findings indicate that Brazilian green propolis displays good anti-ulcer activity, corroborating the folk use of propolis preparations, and contributing for its pharmacological validation.

PMID: 17126509 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17126509

Adv Ther Volume 24 No. 5 September/October 2007 Pgs. 1136-1145

Duration-Dependent Hepatoprotective Effects of Propolis Extract Against Carbon Tetrachloride–Induced Acute Liver Damage in Rats

Monika Bhadauria, PhD, Satendra Kumar Nirala, PhD, Sangeeta Shukla, DSc

Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCl4; 1.5 mL/kg, intraperitoneally)–induced liver damage in rats. Administration of CCl4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCl4 administration, glycogen contents and activities of alkaline phosphatase, adenosine triphosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCl4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=18029340&itool=iconabstr&itool=pubmed_DocSum

Treatment With Purified Propolis Powder (Health Care Food) Against Human Malignant Tumors

Yasuhiro Shimotuura M.D., F.I.C.A.E

The honeybee hive product propolis made by nixing plant resin with bee wax, bee saliva. etc., possesses various pharmacological activities. The use of propolis dates back to ancient Egypt, Greece, and Rome. And in Eastern Europe it has been used as folk medicine for many years. The Bi-Digital O-Ring Test (BDORT) by contrast, would appear to be a more recent discovery. The BDORT can be used to detect the presence of malignant neoplasia in the human body more efficiently than other diagnostic methods such as CT scanning, the fiber scope, and immunological and biochemical tests because it is more sensitive than all of others. The author has administered orally the purified propolis powder (health care food supplied by Hayashibara Biochemical Labs.) every day, prepared by nixing ethanol-extracted propolis with anhydrous maltose, to patients who were found positive for malignant tumor only by the BDORT but negative by other authorized diagnostic tests mentioned as the above, and also to others who were positive for malignant tumor by BDORT and other tests and were waiting for surgical treatment (more than 50 cases). The optimal dose of propolis powder for each patient was determined by BDORT and adjusted frequently due to individual variation. The regression or disappearance of tumors were found clearly in almost all types of patients after two weeks to six months. No side effects have been observed yet.

http://bdort.net/en/5stinter.htm

Components Of Purified Propolis Powder (Health Care Food) And Their Biological Activities

Masashi KURIMOTO
Hayashibara Biochemical Laboratories, Inc.

Propolis, beeglue obtained from bee hives, is known as a home-made remedy against infectious diseases because of its anti-microbial and antiviral effects. We prepared propolis powder adsorbed to anhydrous maltose to facilitate its solubility. This propolis powder has BRM-like effects such as macrophage activation and inhibition or experimental tumor metastases. Recently, a single low molecular weight compound that has strong anti-microbial activity has been purified and identified from Brazilian propolis. The purpose or this investigation was to examine the anti tumor activity of this new component. This component dose-dependently inhibited the in vitro growth of several human and animal tumor cell lines. Anti tumor effects were also observed in and animal cancer model by the intra tumor administration or this component. Histopathologically, large areas or necrosis and tumor cell death were observed in the tumor tissue. Our Propolis powder containing this component that has anti tumor potential, may be useful in human health.
[...]
http://bdort.net/en/5stinter.htm

Virchows Arch. 2001 Mar;438(3):259-70. Related Articles,Links

Pulmonary Carcinogenesis induced by ferric nitrilotriacetate in mice and
protection from it by Brazilian propolis and artepillin C.

Kimoto T, Koya-Miyata S, Hino K, Micallef MJ, Hanaya T, Arai S, Ikeda M, Kurimoto M.

Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki 675-1, Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiolar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar cells after administration of Fe-NTA. These substances disappeared after oral administration of propolis or artepillin C, as shown histochemically, and correlated with an anticancer prophylactic effect of propolis and artepillin C. From our investigation, lipid peroxidation seems to play an important role in pulmonary arcinogenesis. Malignant progression from adenoma of bronchiolar or alveolar origin to malignant tumors has been proposed to involve a stepwise transformation. In our study, adenomas developed into adenocarcinomas and large cell carcinomas after treatment with Fe-NTA. In contrast, after oral administration of propolis or artepillin C, adenomas did not progress to carcinomas. Instead of developing into large cell cancers, as induced by Fe-NTA in control mice, adenomas showed remarkable proliferation of macrophages and local anti-oxidant activity after treatment with either propolis or artepillin C. Propolis and artepillin C therefore appear to inhibit lipid peroxidation and the development of pulmonary cancers.

PMID: 11315623 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11315623&query_hl=17

Propolis, which is a mixed product with material that bees collect from pollens and tree barks, and a secretion of bees, has been traditionally utilized for years as a natural antibiotic and an anti-inflammatory or analgesic in Eastern European countries. The main production center is Brazil, and the form is a dark brown colored wax. At present, most propolis products in Japan are produced by an alcohol extraction method.

Several components isolated from propolis have been shown to have anticancer activity. This study (Anticancer Res 2001 May-Jun;21(3B):1665-71 Luo J, Soh JW, Xing WQ, Mao Y, Matsuno T, Weinstein IB.) demonstrates that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity. Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.

Susceptibility of propolis-treated tumor cells to human natural killer cell activity in vitro

The present study examines susceptibility of Propolis-treated tumor cells to Natural Killer (NK) cell cytotoxicity. Propolis is a resinous substance collected from plants by bees who use it to line hives and fill cracks. Two human tumor cell lines were used in the study: K562, an erythroblastoma which is NK sensitive, and Raji, a Burkitt's cell lymphoma which is NK resistant. Tumor cells were treated with 0.1 mg/ml Propolis for 3 days. Activity of NK-PBL obtained from 10 healthy control subjects was examined against both tumor cell lines using standard (51)Cr-release assay at a ratio of 50:1. Results showed that both tumor cell lines became more sensitive to NK cytotoxicity post treatment with Propolis. K562 cell lysis increased from 37.9% to 57.0% for control and Propolis treated cells respectively, representing a 33.5%, +/- 12.0% increase in lysis. Interestingly, Raji cells became even more susceptible to NK cells after Propolis treatment, with an 81.6%, +/- 8.7% increase in lysis. The increase in tumor cell susceptibility to NK cytotoxicity post treatment with Propolis may represent one mechanism by which Propolis exerts its anti-cancer activity.

Paper presented at the International Symposium on the Impact of Biotechnology on Predictive Oncology and Therapy; Boston, Massachusetts; December 11 - 13, 1994; in the section on Diagnostic Techniques.

· World propolis production is increasing substantially. Major producers include China_,Brazil_,US, Australia and Uruguay.

· Flavonoids account for much of the biological activity in propolis. At least 38 flavonoids have been found in propolis and Brazilian propolis has some of the highest amounts of these essential flavonoids.

· A large number of studies have shown propolis to be highly antimicrobial. Propolis has been found to have an inhibitory affect on at least 21 species of bacteria (including MRSA)₁ 9 species of fungi (including the causative organisms of thrush, ringworm and athlete's foot), 3 species of protozoa (including Giardia)₁ and a range of viruses (including herpes and influenza). (see Section 6.1)

· Propolis has been shown to have a range of other therapeutic properties, including anticancer effects, antioxidant effects₁wound healing and tissue repair effects, gastro-intestinal effects, skin infection effects, anti-inflammatory effects, anaesthetic effects, effects on the immune system, cardiovascular effects and dental care effects. (see Sections 6.2~.12)

· Because of the high levels of flavonoids found in propolis, the product has high value as an antioxidantifree radical scavenger in humans. Of particular interest is its ability to protect vitamin C from being oxidized or destroyed. (see Section 6.4)

· Clinical studies have shown propolis to be effective in the treatment of bronchitis and similar disorders; influenza and herpes; ringworm and skin fungi; a range of dental disorders; skin ulcers, burns and abscesses; ear infections; giardia and colitis, hip inflammation; and vaginal and cervical inflammation. (see Section 7)

· Propolis is known to cause contact dermatitis in a small percentage of humans. The dermatitis has been shown to be relieved once the skin is no longer in contact with the propolis product. It is therefore recommended that usage is ceased whenever there is an allergic reaction. (see Section 8)

· Contamination and short shelf-life is not a problem with propolis and propolis products, because of the substance's antioxidant and antimicrobial properties. Raw propolis should routinely be tested for lead contamination. (see Section 10)

Neuroprotection by Brazilian Green Propolis against In vitro and In vivo Ischemic Neuronal Damage

Masamitsu Shimazawa,¹ Satomi Chikamatsu,¹ Nobutaka Morimoto,^1,2 Satoshi Mishima,³ Hiroichi Nagai,² and Hideaki Hara^1,*

¹Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan ²Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan ³Research Center, API Co. Ltd, Gifu, Japan

^*For reprints and all correspondence: Professor H. Hara, PhD, Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, 502-8585 Japan. Tel: +81-58-237-3931; Fax: +81-58-237-5979; E-mail: hidehara@gifu-pu.ac.jp

ACTIVITY OF PHENOLIC COMPOUNDS ISOLATED FROM BRAZILIAN PROPOLIS AGAINST T. CRUZI

Marcucci, M.C.*, Dantas, A.P.**, Ferreres, F.^§, Bankova, V.S.^#, and De Castro, S.L.**

*Faculdade de Engenharia e Ciências Tecnológicas, Universidade Metropolitana de Santos (UNIMES), **Laboratório de Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, CP 926, 21045-900, Rio de Janeiro, RJ, Brazil, ^§Laboratorio de Fitoquímica, CEBAS (CSIC) Murcia, Spain, ^#Institute of Organic Chemistry with Centre of Phytochemistry, Sofia, Bulgaria

Propolis is a resin collect by honeybees from plant exudates and used to protect the hive. At least 200 compounds were identified in different samples and most of the biological activities of propolis (such as microbicidal, antiviral, and antitumoral) are associated with its phenolic components (Marcucci, Apidologie, 26, 83, 1995). Previous work showed that in vitro ethanolic extracts of commercial resin were active against the three forms of T.cruzi (Higashi & De Castro J. Ethnopharmacol., 43, 149, 1994), but with no efficacy in the treatment of T. cruzi-infected mice, even by oral administration of doses up to 5g resin/kg/day (De Castro & Higashi J. Ethnopharmacol., 46, 55, 1995). These results led us to attempted its fractionation, selection and purification of active(s) principle(s).

Brazilian propolis is extensively used, specially in Japan, in foods and beverages aiming to improve human health, but there are only few reports about its composition and biological activity. We are investigating the phenolic composition of Brazilian propolis and its possible trypanocidal activity. We report the isolation and elucidation of two phenolic compounds - 3,5-diprenyl-4-hydroxycinnamic acid (I) and 2,2 dimethyl-6-carboxyethenyl-2H-l-benzopyrane (II) - from Brazilian propolis (Mandirituba, Paraná State sample #97). Their activity against bloodstream forms of T. cruzi (Y strain) was assayed and untreated and crystal violet (CV)-treated parasites were used as controls. Cell counts were performed after 24 h/4°C and the calculated ED₅₀values were: I: 1.205±0.083 mg/ml, II: 0.770±0.057 mg/ml CV: 0.187±0.021 mg/ml. Compound II was considered a likely candidate to be one of most important components in Brazilian propolis with antibacterial activity (Aga et al., Biosci.Biothech.Biochem. 58, 945, 1994). In our case, both compounds presented lower activity than CV. Since propolis is a complex mixture, its biological activities, in several instances, are due not just to one compound, but to a synergistic action of several components. Other compounds are being chemically characterised for further assays against T.cruzi aiming a more complete analysis of the trypanocidal activity of phenolics isolated from Brazilian propolis.

Mycoses
Volume 48 Issue 3 Page 205 - May 2005
doi:10.1111/j.1439-0507.2005.01128.x

Original article
Comparison of in vitro activities of antifungal drugs and ethanolic extract of propolis against Trichophyton rubrum and T. mentagrophytes by using a microdilution assay
A. N. Koc1, S. Silici2, D. Ayangil1, A. Ferahba3 and S. Çankaya4

Summary

The in vitro activities of propolis against 29 strains of dermatophytes were compared with those of terbinafine, itraconazole, ketoconazole, and fluconazole. Minimal inhibitory concentrations (MICs) were determined according to a National Committee for Clinical Laboratory Standards broth microdilution method. Among the systemic antifungals tested, terbinafine was the most potent. Propolis showed important antifungal activity and it merits further investigation as a potentially useful agent for the treatment of dermatophytosis.

Oct 2002, Vol. 17, No. 5: 553-562

Cancer Biotherapy & Radiopharmaceuticals Antitumor and Anticytopenic Effects of Aqueous Extracts of Propolis in Combination with Chemotherapeutic Agents

Ikukatsu Suzuki Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Ikuo Hayashi Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Takayuki Takaki Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Debra S. Groveman Veterans Administration Hospital, White River Junction, VT 05009, U.S.A Yoshiaki Fujimiya Department of Basic Medical Sciences, IOND University, Tokyo 165-0027, Japan; R&D Department, Nimura Genetic Solutions, Tokyo 151-051, Japan

Using an ICR mouse model bearing a syngeneic Ehrlich ascitis carcinoma, the present study was undertaken to examine the effects of crude, water-soluble propolis (CWSP) on tumor progression, chemotherapeutic efficacy, and hematopoiesis in the peripheral blood. It was demonstrated that CWSP, administered subcutaneously, resulted in marked regression of tumor growth in mice, at the early phase after tumor inoculation (CWSP, p < 0.05 vs. saline control). Molecular analysis indicated that the CWSP is composed of 8.4% protein, 4.2% quercetin plus a variety of saccharides with a molecular weight of 29 kDa. Orally administered CWSP did not produce any regression for the observation period (oral CWSP, p > 0.05 vs. saline control). Peritoneal injection of CWSP into neonatal mice resulted in an increased lymphocyte/polymorphonuclear leukocyte ratio activity, indicating the potential activation of lymphoid cell lineages. These observations suggest that subcutaneously injected CWSP could regulate the development of tumors by possibly stimulating multicellular immunity. In addition, oral administration of CWSP concurrently with 5-fluorouracil (5-FU) or mitomycin C (MMC), significantly increased tumor regression as compared with the respective chemotherapy alone, illustrating the adjuvant effect of orally administered CWSP for tumor regression when combined with chemotherapeutic agents.

To examine further the potential usefulness of CWSP for chemotherapeutic regimens, which induce profound multilineage hematopoietic suppression, mice that received CWSP orally in addition to a 5-FU or MMC were followed for absolute numbers of platelets and white and red blood cells. The oral administration of CWSP significantly ameliorated the cytopenia induced by 5-FU, resulting in recovery of white as well as red blood cell counts (5-FU plus CWSP, p < 0.05 vs. 5-FU alone or water control; white blood cells on day 15, red blood cells on day 25), but no marked effects on platelet counts was observed (5-FU plus CWSP, p > 0.05 vs. 5-FU alone or water control). On the other hand, CWSP significantly reduced all three MMC-induced cytopenias, especially at the later stage of the chemotherapeutic course (after day 30), suggesting repetitive requirements of oral administration of CWSP.

In summary, subcutaneous administration of an aqueous CWSP resulted in marked regression of transplanted tumors. Orally administered CWSP combined with chemotherapeutic agents significantly increased tumor regression and ameliorated the cytopenia induced by the chemotherapeutic agents alone. These results suggest the benefits of potential clinical trials using CWSP combined with chemotherapeutic agents in order to maximize enhanced immunity while potentially minimizing postchemotherapeutic deteriorated reactions.

This paper was cited by:

Japanese Journal of Complementary and Alternative Medicine. 2005, Vol. 2, No. 1: 45CrossRef

[PDF] THE INFLUENCE OF PROPOLIS INGESTION ON REDOX STATE OF HUMAN SERUM ...File Format: PDF/Adobe Acrobat
propolis ingestion on the redox state of HSA from patients under severe oxidative ... Kyoto, Japan), and specimens were stored at –80`C until HPLC analysis. ...
www.apimondia.org/apiacta/slovenia/en/era.pdf -

Institute of Organic Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria. IOCHNP@BGCICT.ACAD.BG

Phytochemical evidence for the plant origin of Brazilian propolis from Sao Paulo state.

Bankova V, Boudourova-Krasteva G, Sforcin JM, Frete X, Kujumgiev A, Maimoni-Rodella R, Popov S.

Propolis and plant secretions from three species, most frequently mentioned as botanical sources of the bee glue in Brazil (Baccharis dracunculifolia, Araucaria angustifolia and Eucalyptus citriodora) have been investigated using GC-MS. Based on chemical evidence, B. dracunculifolia was shown to be the main propolis source in Sao Paulo state. The antibacterial and antifungal activities of all four materials were also tested, the most active being propolis and Baccharis leaf exudate.

Antitumor and Anticytopenic Effects of Aqueous Extracts of Propolis in Combination with Chemotherapeutic Agents

Oct 2002, Vol. 17, No. 5: 553-562
Ikukatsu Suzuki Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Ikuo Hayashi Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Takayuki Takaki Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan Debra S. Groveman Veterans Administration Hospital, White River Junction, VT 05009, U.S.A Yoshiaki Fujimiya Department of Basic Medical Sciences, IOND University, Tokyo 165-0027, Japan; R&D Department, Nimura Genetic Solutions, Tokyo 151-051, Japan

http://www.liebertonline.com/doi/abs/10.1089/108497802760804781;jsessionid=nfop7-DIqYc4?cookieSet=1&journalCode=cbr

Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5.

Despite recent technological advances in vaccine production, most vaccines depend on the association with adjuvant substances. In this study, propolis, which has been attracting the attention of researchers due to its bioactive properties, was evaluated as an immunological adjuvant.

The association of 40mg/dose of an ethanolic extract of green propolis with an inactivated oil vaccine against bovine herpesvirus type 5 (BoHV-5), resulted in a significant increase (P<0.01) in the neutralizing antibody levels, comparing to the bovines that received the same vaccine without propolis. Besides, propolis increased the percentage of animals with high antibody titers (above 32). Phenolic compounds such as artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) and the derivatives of cinnamic acid besides other flavonoid substances were abundant in the propolis extract used, and they could be the main substances with adjuvant action. The effect of the green propolis extract on the humoral immune response can be exploited in the development of new vaccines.

Keywords: propolis, extract, substances, adjuvant, vaccine, propolis extract, green propolis, with adjuvant

Authored by Fischer G, Cleff MB, Dummer LA, Paulino N, Paulino AS,
Vilela CD, Campos FS, Storch T, Vargas GD, Hubner SD, Vidor T. Centro de
Biotecnologia, Universidade Federal de Pelotas (UFPel), Campus
Universitario, Caixa Postal 354, 96010-900, Pelotas, RS, Brazil;
Laboratorio de Virologia e Imunologia, Faculdade de Veterinaria, UFPel,
Campus Universitario, Caixa Postal 354, 96010-900, Pelotas, RS, Brazil.

Published in Vet Immunol Immunopathol. 2007 Jan 14

Immunomodulation produced by a green propolis extract on humoral and cellular responses of mice immunized with SuHV-1.

Despite recent technological advances in vaccine production, most the vaccines depend on the association with adjuvant substances.

This work evaluated the adjuvant capacity of an ethanol extract of green propolis associated to inactivated Suid herpesvirus type 1 (SuHV-1) vaccine preparations. Mice inoculated with SuHV-1 vaccine plus aluminum hydroxide and 5mg/dose of propolis extract presented higher levels of antibodies when compared to animals that received the same vaccine without propolis. The use of SuHV-1 vaccine with propolis extract alone did not induce significant levels of antibodies, however it was able to increase the cellular immune response, evidenced by the increase in the expression of mRNA to IFN-gamma. Besides, propolis increased the percentage of protected animals against challenge with a lethal dose of SuHV-1. The effect of green propolis extract on the humoral and cellular immune responses may be exploited for the development of effective vaccines.

Keywords: propolis, vaccine, extract, propolis extract, cellular immune, green propolis

Authored by Fischer G, Conceicao FR, Leite FP, Dummer LA, Vargas GD,
Hubner Sde O, Dellagostin OA, Paulino N, Paulino AS, Vidor T. Centro de
Biotecnologia, Universidade Federal de Pelotas (UFPel), CP 354,
96010-900 Pelotas, RS, Brazil; Laboratorio de Virologia e Imunologia,
Faculdade de Veterinaria, UFPel, CP 354, 96010-900 Pelotas, RS, Brazil.

Published in Vaccine. 2007 Jan 26;25(7):1250-6. Epub 2006 Oct 18.

Oral candidiasis treatment with Brazilian ethanol propolis extract.

The Brazilian commercial ethanol propolis extract, also formulated to ensure physical and chemical stability, was found to inhibit oral candidiasis in 12 denture-bearing patients with prosthesis stomatitis candidiasis association. Publication Types: Research Support, Non-U.S. Gov't

Keywords:

Authored by Santos VR, Pimenta FJ, Aguiar MC, do Carmo MA, Naves MD,
Mesquita RA. Department of Clinical Pathology and Surgery, Laboratory of
Microbiology, Dentistry School, Minas Gerais Federal University, Campus
da Pampulha, Belo Horizonte, Minas Gerais, Brazil, CEP 31.270-901.
vegneer2003@yahoo.com.br

Published in Phytother Res. 2005 Jul;19(7):652-4.

Pharmacologyonline 3: 467-473 (2006) de Paula et al.
467
SUSCEPTIBILITY OF ORAL PATHOGENIC BACTERIA AND FUNGI TO
BRAZILIAN GREEN PROPOLIS EXTRACT

Alfredo Mauricio Batista de Paula1, Rafael Tomaz Gomes1, Warner Kwasnicka Santiago1, Ricardo Souza Dias2, Maria Esperanza Cortés1, Vagner Rodrigues Santos1.

Laboratory of Microbiology and Biomaterials, Dentistry School, Universidade Federal de Minas
Gerais; 2Food Microbiology Laboratory - Fundação Ezequiel Dias (FUNED) - Belo Horizonte,
Brazil.

Corresponding Author's Contact Details:
Dr. Vagner Rodrigues Santos
Faculdade de Odontologia UFMG
Avenida Antônio Carlos 6627 – Campus Pampulha
Belo Horizonte – Minas Gerais - Brasil – CEP: 31270-901.
Phone: +55 31 34992406 FAX: +55 3134992430
E-mail: vegneer2003@yahoo.com.br

The aim of this study was to investigate the antimicrobial activity of ethanolic extract and fractions of Brazilian green propolis (BGP) collected by bees from Baccharis dracunculifolia against 16 oral pathogenic microorganisms. BGP was examinated by Reversed-Phase High-Performance Liquid Chromatography (RPHPLC) and its absorption spectra was assessed using UV-Spectrophotometer. Identification of flavonoids and other chemical constituents were carried out using authentic standards. Antimicrobial activity was evaluated by agar diffusion and dilution method. The results indicate that all microorganisms tested were susceptible to BGP. None of the essayed fractions (Coumaric acid, Kaempferol, Pinobanskin-3-acetate, Chrysin, Galangin, Kaempferide, and Artepillin C) was more active than the extract, suggesting a synergistic effect of propolis constituents for the antimicrobial activity.

Key words: Green Brazilian propolis, oral pathogens, antimicrobial activity.

Introduction

Propolis is a natural resinous hive product used by the bees to protect the hive against the invasion of microorganisms and is considered to be a natural antibiotic¹. It has also been used extensively in folk medicine by the Brazilian population for several years. Many beekeepers, pharmacists and local laboratories in Brazil produce a great variety of propolis derivatives for medicinal use. Beekeepers commonly chew raw propolis to treat mouth and upper digestive track infections. Available literature indicates that few antimicrobial studies have been carried out using Brazilian propolis and there are only a few reports documenting the chemical constituents and their biological activities² ³. The aim of this study was to evaluate the antibacterial and antifungal activity of Brazilian green propolis extract and fractions against Candida spp., Gram positive and Gram negative oral pathogenic bacteria.

Effects of Propolis Crude Hydroalcoholic Extract on Chromosomal
Aberrations Induced by Doxorubicin in Rats.

Tavares DC, Lira WM, Santini CB, Takahashi CS, Bastos JK.
Universidade de Franca, Franca, São Paulo, Brazil. - Planta Med. 2007
Nov 12 - Pubmed ID: 17999350

Propolis has been reported to display a broad spectrum of biological activities such as anticancer, antioxidant, anti-inflammatory, antibiotic and antifungal properties, among others. There is great interest not only in the determination of the chemical composition of propolis but also in the understanding of the mechanisms related to its therapeutic actions. In this respect, the aim of the present investigation was to study the influence of both simultaneous (6, 12 and 24 mg/kg b. w.) and subacute (12 mg/kg b. w.) treatment with a crude hydroalcoholic extract of propolis on the frequency of chromosome aberrations induced by the chemotherapeutic agent doxorubicin (DXR) in Wistar rat bone marrow cells. HPLC analysis of the crude extract allowed the quantification of the phenolic compounds: caffeic acid, P-coumaric acid, aromadendrin 4'-methyl ether, 3-prenyl- P-coumaric acid (drupanin), isosakuranetin, kaempferide, 3,5-diprenyl- P-coumaric acid (artepellin C), baccharin and 2,2-dimethyl-6-carboxyethenyl-2 H-1-benzopyran. A total of 100 metaphase cells/animal were analyzed for chromosome aberration frequency and 1000 cells/animal were counted to obtain the mitotic index. The results showed that the dose of 12 mg propolis/kg b. w., administered either as a single dose or as subacute treatment, caused a statistically significant decrease in the frequency of chromosome damage induced by DXR compared to the group treated only with DXR. This reduction might be, in part, due to the presence of phenolic compounds in the studied propolis, which are able to capture free radicals produced by chemotherapeutic agents such as DXR.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17999350

Millions in quest for 'miracle cures'

By MASAMI ITO
Staff writer JAPAN TIMES

.........................Propolis is a mixture of resinous substances that bees collect from flowers, trees and bark, combined with some of their own secretions.

"A bee hive is exposed to a lot of poisonous things," says Chiaki Onuma of Nikken Clinic in Shibuya Ward, Tokyo. "But propolis protects the hive from such dangers."

Although there is no scientific proof that propolis actually prevents SARS, its antibiotic properties have long been known. During ancient times, propolis was used in antibacterial and anti-inflammation poultices, as well as by the ancient Egyptians to prevent mummies from decaying.

One of the key qualities of propolis is said to be its efficacy as an antioxidant. It contains the compound flavonoid, which is found in many fruits, vegetables and flowers and is thought to suppress oxidation -- a naturally occurring biological process that may lead to an array of health problems ranging from hardening of the arteries to strokes.

In his 1996 book "Puroporisu -- sono yakko wo saguru (Propolis -- searching for its pharmaceutical effects)," Tetsuya Matsuno, a scientist working in the field of oncology, explains that propolis also is good for burns, allergies like atopic dermatitis -- and even cancer.

"Although there are no doctors who come out and suggest to their cancer patients that they should take propolis, many silently approve," says Onuma.

Although there is no concrete scientific evidence that propolis "cures" cancer, Onuma, a specialist who used to work at the National Cancer Center, says he has seen it work wonders on many occasions -- especially for patients suffering from the side effects of anticancer drugs and treatments.

"Radiation and anticancer treatments weaken the immune system because they decrease the number of white blood cells," says Onuma. "This leaves the patients vulnerable to infection. But propolis helps increase the count of white blood cells, and therefore strengthens the immune system."

So, with these three "miracle cures" whose sales are now riding high -- amino acids, nigari and propolis -- what used to be a niche market for "alternative medicine" aiming at prevention rather than treatment has well and truly joined the mainstream retail world. Onuma explains that, in many ways, such preventative products taken to maintain health as well as cure sickness echo the essence of Chinese medicine.

"People are changing from being dependent on medical treatment by doctors, to protecting their bodies themselves," says Onuma. "You cannot just listen to whatever doctors say. You have to take action yourself."

The Xanthine Oxidase Inhibitory Activity and Hypouricemia Effect of the Propolis in Rats

Fancl Corporation Central Research Laboratory,^a 12-13 Kamishinano, Totsuka-ku, Yokohama 244-0806, Japan and Morikawa Kenkodo Co., Ltd.,^b 2170 Taguchi, Kousa-machi, Kamimashiki-gun, Kumamoto 861-4616, Japan

The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil was measured. The propolis from both place were seen to have XOD inhibitory activity. However, a stronger tendency was shown in the propolis from China. The compounds in each the propolis were measured quantitatively. A great deal of chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis from China, an abundance of p-coumaric acid and artepillin C in the propolis from Brazil. Therefore it was revealed that the propolis compounds are very different depending on their place of origin. The XOD inhibitory activity of these five compounds was measured. Caffeic acid phenetyl ester had the strongest activity, with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD inhibitory activity. We evaluated the hypouricemic effect of propolis from China on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1 h before the test drugs), and measured plasma uric acid values in rats. Oral propolis had a hypouricemic effect 2 h after its administration to oxonate-pretreated rats. These results suggested that a continuous intake of propolis may be effective for the prevention and the treatment of gout and hyperuricemia.

Key words--propolis; xanthine oxidase inhibitor; gout and hyperuricemia; uric acid; oxonic acid

Recent research in Japan and Australia has reveled that advanced cancer of the stomach and bones have been cured successfully. Patients suffering from these kinds of cancer should daily take one tablespoon of honey with one teaspoon of cinnamon powder for one month 3 times a day.

Date: May 12, 2005 05:14 PM
Author: VitaNet Staff (support@vitanet.net)
Subject: Bee Propolis

Bees create propolis by collecting a resinous sap from trees and then mixing it with wax back at the hive. They use this material much the way people use caulk: to seal their homes. Chemically, propolis is exceedingly complex and contains a rich variety of potent terpenes and benzoic, caffeic, cinnamic,and phenolic acids. It's also high in flavonoids, which by themselves may account for many of the benefits attributed to propolis-and some researchers refer to propolis as a type of flavonoid.

One of the most significant medical journal articles described how the caffeic acids in propolis and honey might prevent colon cancer, which kills some 60,000 Americans each year. Chinthalapally V. Rao, Ph.D., of the American health Foundation, Valhalla, N.Y., reported in Cancer Research (Sept.15,1993; 53:1482-88) that these caffeic acids prevented the formation of precancerous tissue in rats after they were exposed to cancer-causing chemicals.

Most medical articles, however, still point to the value of propolis as a powerful, natural antibiotic. That doesn't mean eating propolis will let you throw away your antibiotics - only that you may not need them quite as often.

Why would bees need substances with broad antibacterial and antiviral properties? Any beekeeper will tell you the answer. Bees are very susceptible to bacterial and viral infections, which can destroy hives the way the bubonic plague ravaged Europe in the 17th century.

Two medical journal articles document the activity of propolis specifically against Staphylococcus aureus, the bacterium that causes dangerous and often deadly surgical infections, blood poisoning, and a type of pneumonia. Five to 10 percent of all patients hospitalized in the United States develop such infections, and S. aureus has become resistant to all but one pharmaceutical antibiotic.

In a Chinese study, researchers found that extracts of propolis - specifically, sinapic, isoferulic, and caffeic acids - inhibited the growth of S. aureus (Qiao Z, China Journal of Chinese Materi Medica, Aug. 1991;16:481-2). A European study reported that ethanol extracts from propolis had a "marked synergistic effect" on the anti-staph activity of two antibiotics, streptomycin and cloxacillin, and a moderate effect on several others (Krol W, Arzneimittel-Forschung, May 1993;43:607-9).

Another scientific investigation discovered that propolis inhibited the activity of several streptococcal bacteria species that cause dental caries.Japanese researchers reported that propolis-fed laboratory fats had far fewer caries than those given a regular diet. Propolis protected specifically against Streptococcus mutans and several other strep species (Ikeno K, Caries research, 1991;25:347-51). These strep species are closely related to the germ that causes strep throat.

Propolis works against bacteria in several ways. One study reported that it prevented bacterial cell division and also broke down bacterial walls and cytoplasm, which is how some prescription antibiotics work (Takaisi-KikuniNB, Planta Medica, June 1994;60:222-7).

Perhaps more remarkable is that propolis acts against viruses, which antibiotics do not. A number of medical journal reports have discussed the role of propolisin fighting upper respiratory infections, such as those caused by the common cold and influenza viruses (Focht J, Arzneimittel-Forschung, Aug. 1993;43:921-3). Other investigators have reported that the cinnamic acid extracts of propolis prevent viruses from reproducing, but they worked best when used during the entire infection (Serkedjieva J, Journal of Natural Products, March 1992;55:294-302).

Underpinning many of the benefits of propolis is that some of its components,like the flavonoids and ethanols, function as antioxidant free-radical scavengers. A study published in the Journal of Ethnopharmacology (Jan. 1994;21:9-13)noted that some of the antioxidant phenols in propolis functioned similarly to vitamin E. In another article, researchers described that propolis had anti-inflammatory properties and that it could also prevent blood clots(Drugs Under Experimental & Clinical Research, 1993; 19:197-203).

Resveratrol and Propolis as Necrosis or Apoptosis Inducers in Human Prostate Carcinoma Cells

Christian Scifo,¹ Venera Cardile,² Alessandra Russo,¹ Rosanna Consoli,¹ Carlo Vancheri,³ Francesco Capasso,⁴ Angelo Vanella,¹ and Marcella Renis¹

¹Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology, and ²Department of Physiological Sciences, Viale Andrea Doria, 6 and ³Department of Internal and Specialistic Medicine, Via Passo Gravina 187- University of Catania, 95125 Catania, Italy
⁴Department of Experimental Pharmacology, Via D. Montesano 49, University of Naples Federico II, 80131 Naples, Italy

Vegetables and fruit help the prevention and the therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects of resveratrol (100 and 200 mM), a phytoalexin found in grapes, and of the ethanolic extract of propolis (50 and 100 mmg/ml), a natural honeybee hive product, were tested in androgen-resistant prostate cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma. A comparison between the activity of these micronutrients and vinorelbine bitartrate (Navelbine®), a semisynthetic drug normally used in the therapy of prostate cancer, was conducted. Several biochemical parameters were tested, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), cell redox status (nitric oxide formation, reactive oxygen species production, reduced glutathione levels), genomic DNA fragmentation (COMET assay) with special attention on the presence of apoptotic DNA damage (TUNEL test), and possible mitochondrial transmembrane potential alteration (DY). Our results point out the anticancer activity of resveratrol and propolis extract in human prostate cancer, exerting their cytotoxicity through two different types of cell death: necrosis and apoptosis, respectively. The data obtained suggest the possible use of these micronutrients both in alternative to classic chemotherapy, and in combination with very low dosage of vinorelbine (5 mM).

Key words: Human prostate cancer; DU 145; Resveratrol; Propolis; Vinorelbine

Address correspondence to Dr. Marcella Renis, Associate Professor, Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology, University of Catania, Viale Andrea Doria, 6, 95125 Catania, Italy. Tel: (+39) 095 7384081; Fax: (+39) 095 7384222; E-mail: renis@unict.it

Health Nutrients That Make a Difference
Reprinted from The New Fillmore, San Francisco, April 2003

"…one of the most powerful antibiotics in nature…propolis can protect specifically against staphylococcus aureus, a bacteria that causes serious infection, blood poisoning, and a type of pneumonia…staph a. has become resistant to all but one pharmaceutical antibiotic… New studies show that propolis inhibits the streptococcal bacteria…it performs much like a prescription antibiotic -- preventing bacterial cell division and breaking down bacteria cell structure. Even better, propolis works against viruses, something that antibiotics cannot do."

To this one can add that the human body never develops tolerance to the effects of propolis. Also it is a very strong painkiller and fungicide. Bee propolis has the added benefits of bee enzymes and pollen, making it rich in immune defense nutrients and amino acids. Propolis is thought by some healers to be the one nutrient that can put shingles (herpes zoster) in remission.

Studies & Research News
85 percent of cancer patients take aguricus, a study shows

A study conducted by Prof. Kizu of the Kyouritsu University of pharmacy (www.kyouritsu-ph.ac.jp) for the supplement users in cancer patients under the medical care.

The study was conducted through 74 cancer patients in 32 cancer treatment centers in Japan. The study showed 85 percent of the patients under the medical care are taking aguricus blazei for the supplement, propolis is 55 percent, vitamins is 40, and royal jelly is 32 percent.

82 percent of the pharmacists in those centers said there are no improvements, the patient’s condition by the supplements.

9 percent of the cancer centers suggested to the patients not take the supplements.

80 percent of the doctors in those centers accept the supplement, if the patients prefer to continue to take them, but monitor the condition closely. (The Health Industry News)

YAKUGAKU ZASSHI, 124(11),847-850, 2004

--Notes--
Assessment of Antioxidant Activity of Natural Compound by Water- and Lipid-soluble Antioxidant Factor
Eiji USAMI,*,a Genjiro KUSANO,b Takanori KATAYOSE,c Hiroshi WACHI,c and Yoshiyuki SEYAMAc
Chigasaki Municipal Hospital,a 5-15-1 Honson, Chigasaki 253-0042, Japan, Osaka University of Pharmaceutical Sciences,b 4-20-1 Nasahara, Takatsuki 569-1094, Japan, and Faculty of Pharmaceutical Sciences, Hoshi University,c 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
We evaluated the antioxidant activity of natural compounds in water-soluble and lipid-soluble phases and found that ferulic acid, quercetin and caffeic acid showed stronger activity in the water-soluble phase. Various fractions isolated from Bidens pilosa showed this activity mainly in the water-soluble phase. Antioxidant activity in the lipid-soluble phase of propolis depended on the lipophilic extraction.

Key words--antioxidant activity; Bidens pilosa; propolis

Recommendations for Cancer / Risk Reduction - General Measures: Amino Acid / Protein Tyramine-containing Foods Avoidance

Animal-based
Shark Liver Oil
Propolis / Bee Products Bee propolis, a sticky resin collected by bees from trees, is a COX-2 inhibitor, according to Dr. Gaynor. Dr. Rao has found bee propolis very effective for cancer prevention in animals, noting, "You can use it in lower doses than curcumin because it is highly absorbable." It is typically sold as 500mg capsules.

Botanical
Wormwood When Dr. Rowen discovered a report by Drs. Henry Lai and Narenda Singh, bioengineering professors at the University of Washington, that indicated that the herb "might provide a safe, non-toxic, and inexpensive alternative for cancer patients", he started using it with cancer patients. “Chinese Herb Cures Cancer” by Dr. Robert Jay R Rowen, Second Opinion, May 2002. Dr. Lai and his colleague, Dr. Singh, had found its use dramatically killed breast-cancer cells and leukemia cells while leaving normal breast cells and white blood cells unscathed.

According to Lai, it is believed to work because when artemisinin or any of its derivatives comes into contact with iron, a chemical reaction ensues, spawning charged atoms that chemists call free radicals. Cells need iron to replicate DNA when they divide, and since cancer is characterized by out-of-control cell division, cancer cells have much higher iron concentrations than do normal cells. What Lai did was to pump up cancer cells with even more iron and then introduce artemisinin to selectively kill them. Lai theorizes that more aggressive cancers such as pancreatic and acute leukemia, which are characterized by more rapid cell division and thus higher iron concentrations, may respond even better.

Dr. Rowen also reported on an article that appeared about a year ago in a major cancer journal demonstrating significant artemisinin anticancer activity in a wide variety of laboratory cultured cancer cells. Cancers resistant to common chemotherapy drugs showed no resistance to artemisinin. International Journal of Oncology 18; pp.767-773, 2001

One of the patient's Dr. Rowen worked with was a 47 year old female with stage 4 breast cancer with metastases to the spine.. She used IPT, high-dose nutritional therapy, dietary changes, dendritic cell vaccine, multi-step oxygen therapy, and more. All of her symptoms regressed, but the CT showed no change. When artemisinin derivatives were added, greater results were obtained.

A Dr. Hoang of Hanoi, Vietnam, reports that 50 to 60% of 400 cancer patients have achieved long-term remission utilizing artemisinin together with a comprehensive integrative cancer strategy. Among these patients is a 47 year old female who, presented with terminal liver cancer from hepatitis B and abdominal ascites, was just days or weeks from death. Today; 2 1/2 years later, she is alive and well with no signs of any disease. Dr. Singh is currently following many cancer patients. While not reporting remissions or apparent cures, he says all patients are responding and have at least stabilized. He has found no type of cancer unresponsive to artemisinin derivatives in his studies. Dr. Hoang recommends treatment for two years. Cancer could be like the malaria parasite. If just one cell remains, it can find its way back. Thus, as in malaria, although the parasite is cleared in a few days, prolonged treatment best prevents relapse.

This treatment is said to be non-toxic, so you can continue taking it indefinitely with no expected side effects, though it does depend on the form of artemesia one uses. There are three common artemesia derivatives - Artesunate is water soluble and may be the most active and the least toxic, but it has the shortest life within the body. Artemether is oil or lipid soluble and has the longest half-life. It also has the most toxicity (but this is related to rather high dosages, which are not necessary. Its big advantage is that it can cross the blood-brain barrier to reach cancers in the nervous system. Artemisinin is the active parent compound of the plant. It has an intermediate half-life, is very safe, and also can cross the blood-brain barrier. The first two are slightly altered semi-synthetic derivatives of artemisinin, the concentrated and purified active agent.

Dr. Singh reports that a combination of the forms may be the very best treatment due to these different properties (based on a lab experiment). Thus, he feels the best preparation will contain artemisinin and artemether to provide a dose of 0.5-2 mg/Kg of each form once daily before bed (away from any residual iron left in the stomach from the evening meal). Dr. Hoang used 500mg twice daily of oral artemisinin with good success. The product is best taken on an empty stomach with some natural fat to enhance absorption. Any iron present from residual food may neutralize the peroxides. Milk is one of the few foods with minimal iron. Whole milk, cottage cheese, or yogurt have ample fat to enhance absorption.

Additionally, Dr. Rowen stated that he adds cod liver oil (for its omega-3 and vitamin D) and conjugated linoleic acid (CLA) to this therapy. He says that, with the exception of patients very near death, taking artemisinin or derivatives have stabilized, improved, or remitted every cancer patient he has followed. Medical literature also seems to suggest that oxygenating the system might make the products effective. Administration of certain chemotherapy agents (IPT), which kill cells through free radical mechanisms, is another option.

Artemesia herb products are not the same as the concentrated forms of the derivatives described above. The highest concentration of artemisinin (the active agent) in the raw herb in best of conditions does not even get beyond one-half percent. Dr. Singh tested some products, finding perhaps only 10 to 20% of anti-cancer activity against cultured cancer cells compared to pure artemisinin. Allergy Research Group distributes a high grade artemisinin confirmed by independent lab analysis, so this is the one Dr. Rowen recommended.

Topical artemisinin (one capsule ARG artemisinin in 50% DMSO, BID) has been tried with some success also, so this method, along with internal use, is recommended when the tumor is accessible.

The fact that artemisinin's direct antineoplastic effect- closely resemble that of high-dose intravenous vitamin C is intriguing. The potential benefit of artemisinin in cancer treatment should be further explored because it is simple, safe, well-understood, and capitalizes on the multifold weakness in cancer cells to defend themselves against oxygen radicals. Enhancing the oxidant activity with other oxidation agents (such as carnivora, ultraviolet blood irradiation, H202, or higher oxygen tension itself) may add significant synergism. Adding artemisinin to low dose chemo-therapeutic regimens inducing cytotoxicity via free radical mechanisms (such as doxorubicin), may safely add to the effectiveness of such treatment. Dr. Singh has shared that he has been following a series of cancer patients with nearly universal improvement on artemisinin or its derivatives.

Please note: Dr. Rowen warns that this is not a singular therapy and should be used in conjunction with a comprehensive cancer management strategy, together with the help of an integrative medicine physician or an open-minded oncologist.

Medicinal Mushrooms Antitumor and anticancer properties have been studied in mushrooms. Shiitake (Lentinus edodes) and reishi (Ganoderma ludidum) have been found to have general anticancer and immune-stimulating activity. [Gan To Kagaku Ryoho 1982;9(8): pp.1474-81] Maitake (Grifolia frondosa) also contains immune-stimulating polysaccharides. In a study by Hiroaki Namba, Ph.D., of Japan, mice were fed either a control diet, a diet that included 20% maitake powder or a control diet plus injections of maitake D-fraction extract at a rate of 1mg/kg of body weight. Results showed that maitake inhibited metastasis by 81% in the maitake-fed group and by 91% in the D-fraction injection group.

There are an increasing number of combination mushroom products on the market to help prevent and provide a supportive role in the treatment of cancer.

However, a six month trial of a Shitake extract produced no noticeable benefit in prostate cancer sufferers. [Urology 2002;60(4): pp.640-4]

Coffee Enema Dr. Max Gerson pioneered the use of the coffee enema starting in the 1930s as part of a general detoxification regimen for cancer. Dr. Gerson noted some remarkable effects of this procedure including patients no longer needing pain-killers once on the enemas. The frequency of coffee enemas needed to achieve this effect may be many during a single day, and should not be undertaken without supervision.

Dr. Lee Wattenberg, MD was able to show that substances found in coffee - kahweol and cafestol palmitate - promote the activity of a key enzyme system, glutathione S-transferase. This enzyme is responsible for neutralizing free radicals, harmful chemicals now commonly implicated in the initiation of cancer and needed for detoxification. Consuming coffee orally does not produce the benefits experienced when it is taken as an enema.

When cells are challenged by poisons, oxygen deprivation, malnutrition or a physical trauma they lose potassium, take on sodium and chloride, and swell up with excess water. This “tissue damage syndrome” makes it easier for cancerous cells to survive. Cells normally have a preference for potassium over sodium but when a cell is damaged it begins to prefer sodium.

This craving results in a damaged ability of cells to repair themselves and to utilize energy. Furthermore, damaged cells produce toxins. Around tumors are zones of "wounded" but still non-malignant tissue, swollen with salt and water. Dr. Gerson believed that cancer could not exist in normal metabolism. He directed his efforts toward creating normal metabolism in the tissue surrounding a tumor.

Turmeric Extract, Curcumin Curcumin, the ingredient that gives turmeric its yellow color and one of the best studied of the natural COX-2 inhibitors, has been shown to inhibit the development of cancer in animals. Dr. Chintalapally V. Rao, a scientist with the American Health Foundation in Valhalla, New York, has conducted extensive animal studies with curcumin and notes that while the new drugs "undermine the activity of the COX-2 enzyme, curcumin completely blocks formation of the enzyme itself."
The intriguing evidence of curcumin’s anticancer effects in animal studies has prompted a clinical trial of the compound. Dr. Steven Schiff at Rockefeller University in New York is assessing whether curcumin supplements (250 mg twice a day) can inhibit the development of colon cancer in humans. Much better absorption is achieved when taken with bioperine.

One of the main causes of cancer is chemical-induced changes in DNA resulting in uncontrolled cell reproduction. One of the things that sets curcumin apart from most other anti-cancer supplements is that it can actually block chemicals from getting inside cells. Importantly, curcumin can interfere with pesticides that mimic estrogen, including DDT and dioxin. Curcumin competes for the same chemical doorway as estrogen and estrogen-mimicking chemicals, and as such has the power to block access to the cell and protect the cell from becoming cancerous.

So far, in animal studies, curcumin has been found to block the cancer-causing effect of other chemicals such as paraquat, nitrosamines and carbon tetrachloride.

Curcumin has a number of cytokine-inhibiting properties such as the inhibition of angiogenic signals from tissue-like bone marrow, as well as the down-regulation of pro-inflammatory cytokines such as bFGF and HGF. It increases the expression of functional nuclear p53 protein in human basal cell carcinomas, hepatomas, and leukemia cell lines. This increases apoptosis. It also down-regulates the inflammatory cytokine TNF-alpha in bone marrow stromal cells. Higher doses of curcumin would appear to be useful for cancer patients to take.

In India (where the spice is widely used) the prevalence of the top four U.S. cancers - colon, breast, prostate and lung - is 10 times lower. [Cancer July 11, 2005]

Ginseng, Korean - Chinese / Asian (Panax ginseng) Ginseng is known to reduce the risk of many types of cancers.

MGN3
Bindweed (Convolvulus arvensis) Bindweed inhibits new blood vessel development and thus restricts cancer growth. A typical dose is four to six 250mg capsules per day. Support for its use in cancer is currently limited to laboratory studies and personal experiences.

Herbal Combinations The essential ingredients of "C" Formula and "Y" Formula - CESSIAC(R) and YUCCALIVE(R) - include sheep sorrel, burdock root, schidigera yucca and fennel. The results of this group of observations, conducted in China, showed that the combined use of "C" Formula and "Y" Formula had confirmed therapeutic effect on the treatment and prevention of tumors. They could improve the immunologic function of the body and the overall health of the patient. The herbs had no obvious toxic side-effects. Information and study details can be found at the home page for Focus On Health.

Of the 39 cases in this study, 23 were tumor patients and 16 were secondary immunologic deficiency patients. Among the tumor patients, three died of advanced metastatic carcinoma since they were already at a critical stage when starting the treatment. There was one case of complete remission, 6 cases of partial remission and 13 cases of moderate remission and stabilized development. The total remission rate was 30.4%. The rate of moderate remission and stabilized development was 56.5% and the death rate 13%. Of the 16 secondary immunologic deficiency cases, 5 were notably benefited, 8 were moderately benefited, and three did not benefit.

Notably, there were no toxic side-reactions as seen with other anticancer drugs, such as arrest of bone marrow, digestive tract reactions and baldness. On the contrary, all patients in the study group had improvements in spirit, appetite, digestive function, physical strength and immunologic function of the body. The herbs were also shown to be effective on hepatitis B, allergic rhinitis, pulmonary tuberculosis and coronary heart disease. Therefore, the herbal combination was considered to be better than other antitumor drugs.

Astragalus Root (Astragalus membrinaceus) In studies performed at the Nation Cancer Institute and 5 other leading American Cancer Institutes over the past 10 years, it has been positively shown that astragalus strengthens a cancer patient's immune system. Researchers believed on the basis of cell studies that astragalus augments those white blood cells that fight disease and removes some ot those that make the body more vunerable to it. There is clinical evidence that cancer patients given astragalus during chemotherapy and radiation, both of which reduce the body's natural immunity while attacking the cancer, recover significantly faster and live longer.

Astragalus does not directly attack cancer cells, but strengthens the body's immune system. In the above mentioned studies, both in the laboratory and with 572 patients, it also has been found that Astragalus promotes adrenal cortical function, which also is critically diminished in cancer patients.

Green / Oolong / BlackTea (Camellia sinensis) Green tea can delay or prevent the occurrence of some cancers, but typically must be consumed in large quantities (up to 10 cups or more) daily to achieve this effect. Extracts taken in pill form may be more convenient. There are also teas available with added SGS, which does have an independent cancer preventive action.

Rhodiola Rosea
Garlic
Chlorella / Algae Products
Kelp Kelp and seaweed are anticancer agents, rich in the mucilagenous alginates, which, like most fibers, gums and mucilages, swell in the intestines and absorb liquid as well as toxins and heavy metals. Alginates also may stimulate T cell production and function since numerous other mucopolysaccharides have been shown to do this. Japanese studies show regular consumption of kelp reduces breast cancer risk. Kelp extracts have been highly successful in inhibiting laboratory cancer strains.

Noni
Rosemary (Rosemariana officinalis) Rosemary is a COX-2 inhibitor, and increases the activity of detoxification enzymes. An extract of rosemary, termed carnosol, has inhibited the development of both breast and skin tumors in animals. Rosemary can be used as a seasoning or a tea: Use 1tsp dried leaves per cup of hot water; steep for 15 minutes.

Gravel root (Eupatorium pupureum)

Diet
Increased Fruit/Vegetable Consumption Consumption of fruits is widely accepted as lowering the risk of most common cancers except prostate cancer. Many doctors recommend that people wishing to reduce their risk of cancer eat several pieces of fruit and several portions of vegetables every day. Optimal intakes remain unknown.

Increased Fish Consumption Study subjects who ate two or more servings of fish weekly had a much lower risk for esophageal, stomach, colon, rectum, and pancreatic cancers than those who avoided fish. In fact, the rates of these types of cancer were 30 to 50 percent lower among fish eaters. High fish consumption was also associated with lower risks for cancers of the larynx (30 percent lower risk), endometrial cancer (20 percent lower risk), and ovarian cancer (30 percent lower risk).

The short term (2 week) use of fish oil, late in the course of cancer, provided no noticeable benefits. 1.8gm per day EPA and 1.2gm per day DHA had no effect on appetite, tiredness, nausea, well-being, caloric intake, or nutritional status. [ J Clin Oncol 2003;21(1): pp.129-34]

Cabbage Family Vegetables Cruciferous vegetables will reduce the risk of cancer in smokers, and most likely non-smokers as well.

Vegetarian/Vegan Diet "35 percent of cancer deaths may be related to diet." [The National Cancer Institute booklet "Diet, Nutrition, & Cancer Prevention: A Guide to Food Choices"]

Cancer rates for vegetarians are 25 to 50% below population averages, even after controlling for smoking, body mass index, and socioeconomic status.[1,2] Vegans show even better results. One study found that people who include generous amounts of fruits and vegetables in their daily diets have lower rates of cancers of the lung, breast, colon, bladder, stomach, mouth, larynx, esophagus, pancreas, and cervix compared to people who avoid such foods.[3]

Fruits and vegetables contain antioxidant substances, such as vitamin C, vitamin E, and carotenoids, which protect cells against oxidative damage, which is related to cancer risk and other health problems.[4] The multitude of phytochemicals found in various fruits, vegetables, grains, legumes, and nuts are thought to protect against heart disease and cancer.[5]

Chang-Claude J, Frentzel-Beyme R, Eilber U. Mortality pattern of German vegetarians after 11 years of follow-up. Epidemiology 1992;3:395-401
Thorogood M, Mann J, Appleby P, McPherson K. Risk of death from cancer and ischemic heart disease in meat and non-meat eaters. Brit Med J 1994;308:1667-70
Block G. Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr 1991;54:1310S-4S
Jacob RA, Burri BJ. Oxidative damage and defense. Am J Clin Nutr 1996;63:985S-90S
Craig WJ. Phytochemicals: guardians of our health. J Am Diet Assoc 1997;97:S199-S204

Coconut
Low Fat Diet
Alcohol Consumption Another potent COX-2 inhibitor known as resveratrol is produced in the skin of red grapes, where it protects against oxidation and fungal infections. Resveratrol is found in grape juice and red wine; red Bordeaux and French Cabernets contain a particularly high concentration of the compound. Resveratrol appears to help protect against cancer in at least three ways: It is anti-inflammatory, antioxidant and may prevent cancer cells from progressing to their next stage. Supplements of resveratrol have been reported to contain little or none, based upon testing by Dr. David Sinclair.

Not recommended:
Therapeutic Fasting Extended fasting should be avoided in patients with a current known cancerous condition. This is especially true for those who have experienced significant weight loss. These patients tend to be malnourished already, and further nutrient restriction by fasting would make matters worse.

While fasting may control or resolve non-cancerous tumors, it should not be expected that cancerous tumors will shrink during a fast. With advanced cancer, fasting may hasten death, but bring the benefit of lessening pain and making the patient more comfortable while dying.

Drug
Cytoluminescent Therapy (CLT) Information regarding CLT is being placed in this section because of the wide variety of cancers for which it has been used.

Hydrazine Sulfate Cachexia (wasting) in cancer patients is produced by the cancer cells’ partial metabolism of glucose, which leaves lactic acid as a by-product. The liver expends enormous amounts of the body’s energy converting lactic acid back to glucose. As the cancer grows (and puts out more and more lactic acid) this process is intensified, and the body weakens and wastes away. Hydrazine sulfate works by blocking a liver enzyme that catalyzes the conversion of lactic acid into glucose. This both stops the constant energy drain on the body and robs the tumor of a significant source of energy.

Conventional Drugs COX-2 inhibitor drugs, so-called because they block an enzyme called cyclooxygenase-2 (COX-2), are used to treat the pain and inflammation. There is now compelling evidence that they may also protect against cancer. Mitch Gaynor, M.D., director of medical oncology at the Strang Cancer Prevention Center in New York, notes that suppressing COX-2 may be beneficial because, "the COX-2 enzyme helps make carcinogens much more active once they get into your body. The enzyme also allows cancerous cells to grow new blood vessels."

There may be drug-free alternatives to the synthetic COX-2 inhibitors as close as your spice shelf. Although they do not have as powerful an action, it appears that certain foods are natural inhibitors of the COX-2 enzyme. By incorporating these foods in your diet, you can obtain some of the potential cancer-preventing benefits of the COX-2 inhibitors naturally.

Dipyridamole tends to prevent the attachment of cancer cells flowing in the blood circulation to the endothelium and thus tends to prevent the formation of metastases. Dr. Betty Rhodes (retired) has been disappointed that there has been no followup on this most hopeful indication that she has demonstrated of dipyridamole in treating melanoma. She feels that dipyridamole may be just as effective in treating many other forms of solid malignant tumors.

In a trial referencing the poor response to aspirin ine heart disease and stroke, dipyridamole was added to the treatment protocol and the results were outstanding. Over a two-year period, stroke deaths were decreased by 50%, deaths from myocardial infarction decreased by 38% and deaths from cancer by 25%. [ European Stroke Prevention Study, Lancet, December 12, 1987; pp. 1,371-4]

Environmental
Chemical Avoidance Some chemicals cause cancer in experimental animals. Those chemicals identified as being associated with cancers in humans have all been shown to produce cancer in laboratory animals. In every instance, as least one site of cancer was common to both animals and humans. Chemicals shown to be carcinogenic in at least 2 species of animals should be considered as being likely to present cancer risks to humans.

The list of chemicals known to contribute to the development of cancer in animals and humans is long. As time passes, the list is getting longer, not shorter. Anyone at risk for developing cancer, or with a history of cancer, should strongly consider reducing their repeated exposure to as many synthetic chemicals as reasonably possible.

Extract
Beta 1,3 Glucan Macrophages are an important component of the human immune system. Once they are activated by the Beta 1,3 glucan molecule they become awesome disease destroyers. Besides most pathogens, macrophages can recognize and kill a variety of tumor cells. In fact, any cancer is fair game for an activated macrophage. [M. L. Patchen, Ph.D. Department of Experimental Hematology and Radiation Sciences, Armed Forces Radiobiology Institute]

The initial 9 patients studied had malignant melanoma, adenosquamous carcinoma of the lung, or carcinoma of the breast. Control and experimental lesions were injected: subsequently biopsies were performed at varying intervals for histologic evaluation. Always when glucan was administered intralesionally, the size of the lesion was strikingly reduced in as short a period as 5 days. This reduction was associated with necrosis of the tumor and a monocytic infiltration. In small lesions, resolution was complete, whereas in large lesions, resolution was partial. The amount of glucan injected and the quantity of residual tumor appeared to be related. [NATIONAL CANCER INSTITUTE Medline Unique Identifier:75135679]

Homeopathy
COBAT

Hormone
Melatonin Melatonin has been shown to inhibit several types of cancer, especially hormone-related cancers like breast cancer and prostate cancer. This may be due to its ability to reduce the number of cellular estrogen receptors, which reduces the production of cell-multiplication factors. The immune-modulating properties of melatonin seem to convey additional anti-cancer properties. It has been shown to support the use of interleukin-2 in anti-cancer therapy, especially under conditions of controlled lighting. Many animal studies have demonstrated an increase in tumor growth rates in animals whose pineal glands have been removed.

Various researchers report successes against solid tumors, colorectal cancer, non-small cell lung cancer, brain metastases, glioblastoma, estrogen receptor-negative breast cancer, prostate cancer, metastatic renal cancer and adenocarcinoma of the pancreas. Furthermore, these effects seem to be substantial.

To select a typical example, people with solid tumors were given either just IL-2 (a regulator of the immune system), or IL-2 plus melatonin. 15% of the people receiving just IL-2 survived after one year, whereas 46% of the people also receiving melatonin survived. One researcher reported no failures i.e. instances in which melatonin did not have a positive effect. It has been proposed that melatonin might be useful for treating the general ill health found in cancer.

DHEA

Lab Tests/Rule-Outs
Digestive Enzymes / (Trial) Dr. William Kelley recommended high amounts of pancreatic enzymes - 45,000 mg orally. His formula includes a starch-dissolving enzyme which Kelley believes is important in some cases. Many other alternative doctors also use pancreatic enzymes in treating / controlling cancer.

As a large cancer mass is being disolved from enzyme use, it becomes harder for the body to remove this 'waste' material and toxemia can result. Toxemia is the primary reason to have the malignant tumor mass surgically removed when possible.

Test AMAS (AntiMalignin Antibody Screen)
Test Copper Levels
Test Essential Fatty Acid Profile

Mineral
Selenium Selenium is useful in the prevention of several cancers. As deficient selenium levels are associated with an increased risk of cancers in general, ensuring adequate selenium intake and maximizing selenium status in the presence of an elevated cancer risk is highly recommended.

Cesium There are theoretical reasons and experimental findings that indicate fast-growing cancers can be completely resolved by using a 6gm cesium chloride salt for 30-days. Dr. A. Keith Brewer ((1984) had a program for raising the pH of the cancer cell to 8.0 (highly alkaline). This is the same pH in the small intestine, and it is the pH required to activate trypsin’s digestive enzyme activity. (The author has noted that stomach, colon and rectal cancer are all common - small intestine cancer is rare.)

Cesium is way less expensive than quality pancreatic enzymes. A much smaller does of pancreatic enzymes (maybe 4,500mg daily) along with 6,000mg cesium chloride daily might be enough to destroy tumors.

The Brewer cesium protocol includes:

6gm cesium chloride (2000mg A.M., 2000mg noon, and 2000mg evening)
100,000 IU Vitamin A
Up to 30,000mg Vitamin C
Selenium - 200 to 400mcg
Zinc - 50mg
Laetrile (apricot seed extract) - 150 -200mg

Calcium-D-Glucarate

Miscellaneous
Reading List How to Fight Cancer & Win from Agora Health Books contains many unconventional cancer treatments that have helped eliminate cancers of various types. Discover 43 simple ways to cancer-proof your life.

Nutrient
CoQ10 (Ubiquinone) There are sound theoretical reasons to add 400 mg of highly absorbable CoQ10 to any anti-cancer protocol. This dosage has initiated complete tumor regression in breast cancer patients. As the pancreas has a high concentration of CoQ10, it may be that restoring CoQ10 levels improves pancreatic function, which can help prevent and treat cancer, according to the John Beard theory of cancer.

Lycopene A review of 72 studies [J Natl Cancer Inst 1999;91: pp.317-31] reported 57 associations between tomato intake or blood lycopene levels and decreased risk of cancer. Of these associations, 35 were statistically significant. The benefit was strongest for prostate, lung, and stomach cancers, although protective associations were also found for cancers of the pancreas, colon, rectum, esophagus, oral cavity, breast, and cervix. Because the data were from observational studies, a cause-and-effect relationship cannot be firmly established. However, the consistently lower risk of cancer associated with higher consumption of lycopene-containing tomatoes, provides a strong foundation for further research on lycopene.

One study found that for the 25% of people with the greatest tomato intake, the risk for cancers of the gastrointestinal tract was 30-60% lower, compared with those who ate fewer tomatoes. These reduced risks were statistically significant. [Int J Cancer 1994;59: pp.181-4]

Oxygen / Oxidative Therapies
Ozone / Oxidative Therapy

Vitamins
Vitamin D Evidence of vitamin D's protective effect against cancer is compelling. For more than 50 years, documentation in medical literature suggests regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests this is a causal relationship that acts through the body's vitamin D metabolic pathways. For instance, some evidence points to a prostate, breast and colon cancer belt in the United States, which lies in northern latitudes under more cloud cover than other regions during the year. Rates for these cancers are two to three times higher than in sunnier regions.

Dark-skinned people require more sun exposure to make vitamin D. The thickness of the skin layer called the stratum corneum affects the absorption of UV radiation. Dark human skin is thicker than white skin and thus transmits only about 40% of the UV rays for vitamin D production. Darkly pigmented individuals who live in sunny equatorial climates experience a higher mortality (not incidence) rate from breast and prostate cancer when they move to geographic areas that are deprived of sunlight exposure in winter months. The rate of increase varies, and researchers hesitate to quote figures because many migrant black populations also have poor nutrition and deficient health care that confound statistics somewhat.

Although excessive sun exposure may give rise to skin cancer, researchers as early as 1936 were aware that skin cancer patients have reduced rates of other cancers. One researcher estimates moderate sunning would prevent 30,000 annual cancer deaths in the United States.

Vitamin D may also go beyond cancer prevention and provide tumor therapy. Much has been made of pharmaceutical angiogenesis inhibitors - agents that help inhibit the growth of new, undesirable blood vessels that tumors require for nutrient supply and growth. Laboratory tests have shown vitamin D to be a potent angiogenesis inhibitor.

Vitamin D also works at another stage of cancer development. Tumor cells are young, immortal cells that never grow up, mature and die off. Because vitamin D derivatives have been shown to promote normal cell growth and maturation, drug companies today are attempting to engineer patentable forms of vitamin D for anti-cancer therapy.

Vitamin C (Ascorbic Acid) Most of the data shows that high intakes of vitamin C reduce the risk of genetic damage to DNA, lipids and proteins and thus reduce the risk of cancer. Vitamin C may also help prevent cancer by its antiinflammatory effect. [Am J Clin Nutr. 2003; 78: pp.1074-1078]

High dose vitamin C doesn't cure or digest cancer, but according to former Linus Pauling associate Matthias Rath, MD, the following protocol restricts or halts the growth of malignant tumors by deactivating an enzyme. The Rath therapy is thought to interfere with the enzyme that cancer tumors emit, malignin, which allows the tumor to “eat” through ordinary tissue. Malignin is the mirror image of trypsin, the enzyme used in many cancer treatment programs.

The daily protocol from Dr. Matthias Rath is reportedly:

14,000mg Vitamin C
12,000mg Lysine
2,000mg Proline
1,000mg Green Tea Extract (EGCG)

Vitamin Folic Acid

Introduction

Propolis is manufactured by bees from the sap of trees and flower blossoms. Propolis protects the beehive from penetration of harmful insects and aids in insulating the beehive, and maintaining a sterile environment.

Many studies have proven propolis' effectiveness in fighting viruses, bacteria and fungi, and as an anti-inflammatory agent. Propolis is known as Nature's Antibiotic, capable of fighting pathogenic (disease causing) bacteria, as opposed to conventional antibiotics which destroy all the body's natural flora. In addition, bacteria do not become resistant because many natural factors (the sap source, climate and geographical region) all indiscernibly yet significantly continually alter the
natural composition. Propolis strengthens the body's resistance to winter's ailments: infections, flu and colds. Propolis can be used externally to heal cuts, torn tissues and burns (up to second degree) and for surgical scars. Propolis has been found to be effective in the treatment of gum and mouth infections. It has been used for centuries as a folk remedy and has only in recent years been "rediscovered" by science resulting in comprehensive research regarding the active ingredients of propolis and its antibacterial properties [1].

Caffeic Acid Phenethyl Ester (CAPE) Prevents Tumors in Min/+ Mice and Regulates p53 Function In Vitro

by A.M. Carothers, C. Chiao et al, Strang Cancer Prevention Center, NYC

CAPE is a phenolic antioxidant derived from honey bee propolis which decreased tumor formation in the mice used, by 63%. The authors then used human colon carcinoma cells (cancerous) and these showed a decrease as well. - - - - - - -

Radioprotection and Anti Cancer Effects of the Hatakeshimeji (Lyophyllum decastes)

Yeunhwa Gu1, Masayuki Tajima1, Yuuichi Ukawa2, Ikukatsu Suzuki 1, Kenichi Bamen1 and Mitubana yuicti1
1Graduate School of Health Science, Suzuka University of Medical Science,1001-1 Kishioka-cho, Suzuka-shi, Mie 510-0293 Japan
2Oji Forestry & Landscaping Co., Ltd. 4-9-8, Ginza, Tyououku, Tokyo 104-0061 Japan

FOCUS ON PROPOLIS:

Travels to Brazil last year revealed huge interest in an up-and-coming, new, yet old, honey bee product, propolis. The word means "before the city," and presumably originates from the habit of some honey bee colonies that erect curtains of the material at their nest entrance. This presumably reduces the opening, weatherproofing a colony against cold winds and rain. Apis mellifera caucasica has a reputation for gathering the largest amount of the material, but all other races collect it as well.

Propolis is "bee glue," and is the bane of beekeepers because it often causes headaches in inspecting and manipulating hives. In the hot summer it is sticky and difficult to remove from clothes, gloves and tools. In cooler weather it becomes hardened and easily cracks during manipulation, which can increase defensive behavior.

Honey bees use propolis to caulk cracks in and varnish the interior of their hive. This is not lost on the violinmakers in Cremona, Italy, who, like the

famous Stradivarius before them, continue to use the material in finishing their instruments.

Evid Based Complement Alternat Med. 2005 March; 2(1): 29–32.
doi: 10.1093/ecam/neh059.
Copyright © The Author (2005). Published by Oxford University Press. All rights reserved.

Recent trends and important developments in propolis research
Vassya Bankova

Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

For reprints and all correspondence: Vassaya Bankova, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. Tel: +359-2-9606-149; Fax: +359-2-8700-225; E-mail: bankova@orgchm.bas.bg

Received September 30, 2004; Revised December 8, 2004; Accepted December 24, 2004.

The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org

This article has been cited by other articles in PMC.
Top
Abstract
Introduction
The Problem of Chemical Variability of Propolis
Important Trends and Developments in Recent Propolis Research
Conclusion
References Abstract
The newest developments in propolis pharmacological research are summarized. The problem regarding biological studies, caused by the chemical variability of propolis, is discussed. The most important trends and developments in recent propolis research are outlined: biological studies performed with chemically characterized samples, bioassay-guided studies of active principles and comparative biological studies of propolis of different origin and chemical composition. These types of studies are extremely valuable with respect to propolis standardization and practical applications in therapy. They will allow scientists to connect a particular chemical propolis type to a specific type of biological activity and formulate recommendations for practitioners.

Keywords: propolis, plant origin, bioactive compounds, composition/activity relationship

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1062152

Source: University Of Rochester Medical Center

Date: 2001-08-30
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Dentists Abuzz Over Cavity-Prevention Potential Of Honeybee Product

Dentists from the University of Rochester Medical Center and food scientists at State University of Campinas in Brazil have discovered that a substance that Brazilian honeybees make to protect their hives might prove to be a potent anti-cavity agent.

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Related sections: Health & Medicine
Plants & Animals

The substance is propolis, a sticky material like glue that bees make to hold their hives together. Bees create the brew by collecting secretions from trees and other plants, carrying them back to the hive, chewing up the materials, then spitting the concoction out and mixing it with beeswax. In a hive, the substance is used to seal holes, keep the hive clean, and even to embalm dead insects.

In laboratory tests, the most potent version of the substance, from southern Brazil, cut the cavity rate in rats by about 60 percent, and nearly stopped the activity of a key enzyme that forms dental plaque. Dentists say that since rats get cavities the same way as humans do, and the same substances that prevent cavities in the animals also prevent cavities in humans, they’re enthusiastic about the potential of the substance to prevent cavities in people. Dentists hope to test the substance on human volunteers.

The link between hive and health was first noted by Michel Hyun Koo, D.D.S., Ph.D., who earned his dental degree in Brazil and then decided to study food biochemistry. Thanks in part to active honeybee research across campus at State University of Campinas, Koo began studying propolis and soon was traveling around Brazil collecting the material from hives, using a device like a putty knife to scrape the dark yellow or brown, caulk-like substance from hives. His first experience left him barely able to walk, as he received about two dozen stings around his ankles from angry bees because his black socks triggered the bees’ defensive behavior.

Brushing the pain aside, Koo persisted, focusing on the cavity-fighting potential of propolis as he earned his master’s degree in food science and his doctorate in oral biology in Brazil. Then he came to the Center for Oral Biology at the University of Rochester to try to pinpoint the most effective cavity-fighting substances in propolis. Koo was recognized this summer by the International Association for Dental Research, which awarded him its Research in Prevention Award for research in North America at its annual meeting; he received the same award, for research in South America, in 1998 for his earlier work.

“The potential with these natural products is enormous. The bees are doing a great work for human health, by facilitating the identification of compounds with applicability to dental science,” says Koo.

The team isn’t the first to note the health effects of propolis. Human use of propolis dates back to at least 300 B.C., and today there are creams, lotions, and even chewing gum that contain propolis and tout its anti-bacterial, anti-inflammatory, and anti-oxidant properties. In recent times people have claimed that the substance is useful in wound healing, tissue regeneration, and for treating burns, psoriasis, and herpes. Propolis is used as a food additive in Japan, and demand is strong in Europe too; in the United States, Koo says, there has been little demand, though lately he has seen propolis popping up on store shelves, as anti-oxidant capsules or as a solution to treat cuts.

But not all propolis is created equal; the quality and make-up of propolis varies dramatically, depending largely on the plants and trees of the region where honeybees do their work. Koo analyzed more than 2,500 propolis samples from Brazil alone and found 12 different chemical compositions.

“There is a huge variability in terms of chemical composition, depending on the plant ecology of the specific regions where bees collect this material. Just because there’s propolis in toothpaste doesn’t mean it’s useful,” says Koo, noting that there are a few mouth washes and toothpastes that contain propolis. “There’s a huge variety of propolis out there, and much of it is useless against cavities.” That’s why Koo’s colleagues in Brazil are working with beekeepers there to create international standards for propolis.

During the past two years Koo has spent thousands of hours in his Rochester laboratory, working with dental research William Bowen, D.D.S., Ph.D., to figure out exactly which of the more than 100 compounds in propolis are responsible for its cavity-preventing properties. They have found two substances, both present in the potent propolis made by bees in southern Brazil, that seem especially protective. The University of Rochester and State University of Campinas have filed for patents on the compounds, which target both the bacteria that form cavities as well as the specific enzymes that take part in the process.

Dentists are most excited by the action of one of the substances against glucosyltransferase (GTF) enzymes, which play an important role in the buildup of plaque on teeth. The enzymes create molecules called glucans to construct a biofilm, and, like masons at a construction site, they use the glucans like bricks to form a formidable structure that serves as a sort of safe harbor for bacteria to collect, latch onto teeth, and secrete acid that eats away at our enamel. This whole assembly, a biofilm not much different than the slime on a boat hull, is what we call plaque, says Bowen.

“Once this mesh of sugars and bacteria forms, it becomes easier for other bacteria to stick to it. More bacteria join in, and the plaque becomes one big acid factory. It’s like an acid sponge sticking to your tooth’s surface,” Bowen says.

Knocking out the enzymes that build plaque is a key to oral health, Bowen says. Within seconds after brushing your teeth or having them cleaned professionally, GTF enzymes mount an assault on a tooth, creating a biofilm that other bacteria latch onto. Even the nearly one liter of saliva that our body sends washing over our teeth every day isn’t enough to neutralize plaque.

Koo and Bowen found that one of the substances they isolated is the best inhibitor of GTFs that scientists have ever seen. The substance is especially effective at blocking the enzyme that the most common pathogen in our mouth, Streptococcus mutans, uses to build plaque, and it also blocks a particular GTF enzyme that no other compound is known to inhibit. The substance blocked up to 95 percent of the action of GTFs in the test tube and about 60 to 70 percent on tooth-like surfaces, accounting for its effectiveness at reducing cavities in animals.

In addition to Koo and Bowen, the research team includes dental researcher Anne Vacca Smith and research associate Sylvia Pearson of Rochester, dental researchers Pedro L. Rosalen and Jaime A. Cury of State University of Campinas in Brazil, and food scientist Yong K. Park of State University of Campinas.

The work was funded by the National Institute of Dental and Cranio-Facial Research and the Brazilian Government Agency.

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This story has been adapted from a news release issued by University Of Rochester Medical Center.

"TRENDS in PROPOLIS RESEARCH and MARKET in JAPAN. - Matsuka Mitsuo (1998) (Japan)

The following article was postered at the 4th Conference of Asian Apicultural Association, which was held in Kathmandu, Nepal through 23
to27 March, 1998. PRA is a Japanese domestic association at the moment, but I suppose it should be acting internationally soon.

TRENDS IN PROPOLIS RESEARCH AND MARKET IN JAPANMATSUKA, Mitsuo
Propolis Researchers (J Association c/o Faculty of Agriculture,Tamagawa Univ., Machida-shi, Tokyo 194-8610

Propolis Researchers' Association was established in November, 1997.

In the first seminar, two Brasilian professors and two Japanese gave talks on production, nature and application of propolis in past and in
future.

Disconnection among researchers, producers, and consumers was pointed and future activities of the association was promised to offset the gap.

Consumption of propolis in Japan has increased rapidly during a decade, pararelling with the advances of research on propolis.

Japan Propolis Association, composed of ca. 200 member companies, celebrated 10 years anniversary of the establishment in 1997, has their standard for the alcohol extracts, but is struggling with water soluble propolis products.

Colaboration will be needed throughout the world, especially among the researchers themselves and organizations such as Apimondia and other domestic associations in the concerned countries.

E-mail: mmat@agr.tamagawa.ac.jp
Mitsuo Matsuka
Honeybee Science Research Center
Tamagawa University, Machida-shi, Tokyo 194-8610 Japan
Phone & Fax 81-427-39-8685
Web-site: http://www.tamagawa.ac.jp/HSRC/index.html "

= Science and study of the benign tumours and malign tumours (cancers) + diseases caused by radiation.

ONCOLOGY NURSING FORUM
November 2004, Volume 31, Number 6

ONLINE EXCLUSIVE
Herbs or Natural Products That Protect Against Cancer Growth

Part Three of a Four-Part Series
Muriel J. Montbriand, PhD, RN

Propolis has no scientific name. The resinous material from poplar and conifer buds, propolis is used to treat numerous infections such as tuberculosis and those of bacteria, fungal, and protozoal origins. Individuals also self-medicate with propolis for nasopharyngeal carcinoma (Foster & Tyler, 1993). Propolis contains caffeic acid phenethyl ester, which is thought to have cancer chemopreventive activities (Lee et al., 1999). Allergic reactions to propolis are possible, especially in those who are allergic to bees or bee stings. Oral ulcerations may occur from propolis-containing lozenges (Facts and Comparisons, 2001; Hay & Greig, 1990). No typical doses have been reported.

Neuroprotection by Brazilian Green Propolis against In vitro and In vivo Ischemic Neuronal Damage.
Shimazawa M, Chikamatsu S, Morimoto N, Mishima S, Nagai H, Hara H
Evid Based Complement Alternat Med. 2005 Jun;2(2):201-207.

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective function in vitro and/or in vivo. In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H(2)O(2)) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In mice in vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function against in vitro cell death and in vivo focal cerebral ischemia. [Abstract/Link to Full Text]

Evid Based Complement Alternat Med 2005 Mar;2(1):85-92. Epub 2005 Jan 6.
PMID: 15841282 [PumMed - Publisher]

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological effects, such as anti-microbial, anti-inflammatory and anticancer. Shoot apices of Baccharis dracunculifolia (alecrim plant, Asteraceae) have been pointed out as sources of resin for green propolis. The present work aimed (i) to observe the collecting behavior of bees, (ii) to test the efficacy of histological analysis in studies of propolis botanical origin and (iii) to compare the chemistries of alecrim apices, resin masses and green propolis. Bee behavior was observed, and resin and propolis were microscopically analyzed by inclusion in methacrylate. Ethanol extracts of shoot apices, resin and propolis were analyzed by gas chromatography/mass spectroscopy. Bees cut small fragments from alecrim apices, manipulate and place the resulting mass in the corbiculae. Fragments were detected in propolis and identified as alecrim vestiges by detection of alecrim structures. Prenylated and non-prenylated phenylpropanoids, terpenoids and compounds from other classes were identified. Compounds so far unreported for propolis were identified, including anthracene derivatives. Some compounds were found in propolis and resin mass, but not in shoot apices. Differences were detected between male and *female apices and, among apices, resin and propolis. Alecrim apices are resin sources for green propolis. Chemical composition of alecrim apices seems to vary independently of season and phenology. Probably, green propolis composition is more complex and unpredictable than previously assumed.

2: de Lima DC, Alvarez Abreu P, de Freitas CC, Santos DO, Borges RO, Dos Santos
TC, Mendes Cabral L, Rodrigues CR, Castro HC
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15841277&dopt=Abstract
Snake Venom: Any Clue for Antibiotics and CAM?
Evid Based Complement Alternat Med 2005 Mar;2(1):39-47.
PMID: 15841277 [PumMed - Publisher]

"The latest FDA-approved drug for fighting colon cancer [Celecoxib] may be sitting in your kitchen. Rosemary, turmeric, grapes, a honey bee product called propolis: These all contain chemicals similar to a drug used to prevent the growth of cancerous cells in the large intestine; they work much in the same way." It is interesting that the FDA approved the drug, but not the natural substances that contained a natural version of the synthetic drug. See the book: Beyond Aspirin: Nature's Answer to Arthritis, Cancer & Alzheimer's Disease

http://www.google.co.uk/search?hl=en&q=brazilian+propolis+clinical+trials+cancer&btnG=Search&meta=

http://www.google.co.uk/search?q=propolis+cancer+japan+&hl=en&lr=&start=50&sa=N

Propolis Demonstrates Liver Protectant Activity
View 052514-216 9/24/2002	Propolis Demonstrates Liver Protectant Activity	Banskota AH, Tezuka Y, Adnyana IK, Ishii E, Midorikawa K, Matshushige K, Kadota S Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis Phytomedicine 2001; 8 16-23

Propolis Found to have Potential Antimicrobial Activity
View 050142-261 7/30/2004	Propolis Found to have Potential Antimicrobial Activity	Ugar A, Arslan T An in vitro study on antimicrobial activity of propolis from Mugla Province in Turkey Journal of Medicinal Foods 2004;7(1) 90-94

Propolis Ointment More Effective For Genital Herpes Than Acyclovir - Clinical Study
View 092208-191 3/6/2001	Propolis Ointment More Effective For Genital Herpes Than Acyclovir - Clinical Study	Vynograd N, Vynograd I, and Sosnowski Z A comparative multi-centre study of the efficacy of propolis, acyclovir, and placebo in the treatment of genital herpes (HSV) Phytomedicine Vol. 7(1) 1-6

PROPOLIS WHAT IS IT?

Propolis Research Table of Contents

Quality Control

Abstract

Graphical abstract

Abstract

Graphical abstract

Article in Press, Corrected Proof

Susceptibility of propolis-treated tumor cells to human natural killer cell activity in vitro

This paper was cited by:

The Xanthine Oxidase Inhibitory Activity and Hypouricemia Effect of the Propolis in Rats

Health Nutrients That Make a Difference
Reprinted from The New Fillmore, San Francisco, April 2003

FOCUS ON PROPOLIS:

ONCOLOGY NURSING FORUM
November 2004, Volume 31, Number 6

ONLINE EXCLUSIVE
Herbs or Natural Products That Protect Against Cancer Growth

Part Three of a Four-Part Series
Muriel J. Montbriand, PhD, RN

PROPOLIS WHAT IS IT?

Propolis Research Table of Contents

Quality Control

Abstract

Graphical abstract

Abstract

Graphical abstract

Article in Press, Corrected Proof

Susceptibility of propolis-treated tumor cells to human natural killer cell activity in vitro

This paper was cited by:

The Xanthine Oxidase Inhibitory Activity and Hypouricemia Effect of the Propolis in Rats

Health Nutrients That Make a Difference Reprinted from The New Fillmore, San Francisco, April 2003

FOCUS ON PROPOLIS:

ONCOLOGY NURSING FORUM November 2004, Volume 31, Number 6 ONLINE EXCLUSIVE Herbs or Natural Products That Protect Against Cancer Growth Part Three of a Four-Part Series Muriel J. Montbriand, PhD, RN

Health Nutrients That Make a Difference
Reprinted from The New Fillmore, San Francisco, April 2003

ONCOLOGY NURSING FORUM
November 2004, Volume 31, Number 6

ONLINE EXCLUSIVE
Herbs or Natural Products That Protect Against Cancer Growth

Part Three of a Four-Part Series
Muriel J. Montbriand, PhD, RN