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Join Dr. Cass Ingram in the remote Canadian wilderness on a mission to find chaga and to help the human race to be healthier and more powerful than ever. Discover how he locates and extracts this precious forest cure. More can be found in his book The Cure is in the Forest.

The most potent Grade A chaga is found deep in the Siberian forests.


The art of medicine consists of amusing the patient while nature cures the disease. 
- Voltaire

The doctor of the future will give no medication, but will interest his patients in the care of the human frame, diet and in the cause and prevention of disease.
- Thomas A Edison

...the estimated total number of iatrogenic deaths—that is, deaths induced inadvertently by a physician or surgeon or by medical treatment or diagnostic procedures— in the US annually is 783,936.......while 553,251 died of cancer.
- Gary Null, et al., Death by Medicine



Biologically Active Compounds from
Aphyllophorales (Polypore) Fungi

Independent In-Depth Review of

“Inonotus Obliquus” 


Documented for over 5000 years!

What does Chaga do?

Ø  Chaga is anti-cancer,  anti-tumor,  anti-yeast,  anti-parasitic,  anti-bacterial, anti-viral,  anti-fungal,  anti-inflammatory, anti-aging  and anti-pain.

Ø  Chaga belongs to the group of herbs distinguished as “adaptogens”

Ø  Increases the body's resistance to stresses such as trauma, anxiety and bodily fatigue

Ø  Chaga helps to reestablish the electrical grid, allowing the body to self-heal and function correctly and restore cellular communication.

Ø  Chaga is a powerful anti-aging, restorative and cardiovascular supplement

Ø  ability to balance endocrine hormones and the immune system, and they help the body to maintain optimal homeostasis (balance)

Ø  uniquely high in gene-protecting pigment complexes including melanin, and in antioxidants

Ø  Chaga rejuvenates  organs of the body: brain, lungs, heart, stomach, liver and kidneys 

Ø  The polysaccharide beta-glucan,  present in Chaga, is proven to be an effective immune modulator by triggering immune system response

Ø  Chaga has decreased the HIV virus to undetectable and returned T-cell count to normal

Ø  Chaga is effective in gastrointestinal, breast, uterine, leukemia, liver, tumor and other cancers

Ø  Chaga balances the thyroid and helps with type 1 and 2 diabetes

Ø  Chaga is effective against influenza, acid reflux and melanoma

Ø  40,000 times more potent in antioxidants than the closest natural product in foods or essential oils

Ø  Chaga is most powerful when harvested and wild crafted from the forests of Siberia

Ø  Chaga is effective in the form of an extract w/o alcohol not powdered or in tea form


                                                            This independent review of Chaga has not been evaluated by the FDA

                                                                     and is not intended to diagnose, treat or cure any disease.

                                                                                 Please consult a physician if you are ill.

What is in Chaga?

Siberian Chaga is a superior grade medicinal mushroom containing over:

·        215 phytonutrients  plus:

·        Melanin

·        Betulinic acid

·        29 Beta glucans

·        Saponins

·        Polysaccharides

·        SOD antioxidants

·        Triterpenes

·        Inotodiols

·        Organic minerals

·        Amino acids

·        Polysaccharides to enhance the immune system treat cancer, HIV virus, and other anti-bacterial and viral infections.

·        Betulinic acid to counter viral infections and tumors.

·        Triterpenes to lower cholesterol, improve digestion, detoxify the liver, treat hepatitis, chronic bronchitis, coughs and asthma.

·        Germanium to cleanse the blood, normalize blood pressure and prevent tumors.

Other nucleosides, phytonutrients, minerals and amino acids such as

·        Saponin,

·        Iron,

·        Magnesium,

·        Chromium,

·        Beta glucan,

·        Inotodiol,

·        Isoprenoid and others

Siberian Chaga contains an extraordinary amount of SOD (Super oxide dismutase) antioxidants that absorb free radicals and neutralize them before they can damage body tissue cells. Chaga contains 25-50 times more SOD antioxidants than other medicinal mushrooms.

Dear Friend,

Please take time to read this information through to the end. It has saved many lives and is one of the "hidden" wonders of the healing world and the number one anti-aging natural extract available today.

Here is the best product I have found. Wild crafted Siberian Chaga distributed exclusively by Chaga International. (Chaga International in no way is associated with this independent report)

Chaga is a fungus that grows on birch trees over 5 to 7 years. It produces a woody growth called a ‘conk’ that absorbs nutrients from the entire tree, including the tree’s life-energy. In turn, that life-energy is delivered to the person who consumes it. Chaga in the non-animal kingdom is what most resembles human DNA. It contains at least 215 phytonutrients, making it one of nature's most nutritionally-dense foods. It is on the WHO's (World Health Organization) GRAS (Generally Regarded As Safe) list and is classified as one of approximately 250 medicinal mushrooms. It commands 5 to 8 times the value of any other medicinal mushroom.

It has been documented that chaga was used in Asian folk medicine over 4,500 years ago to maintain a healthy life-energy (chi). In 1991, "the Iceman," a man frozen in ice for approximately 5,300 years, was found in the Alps with a pouch of chaga on him. Chaga has been used traditionally as a health-promoting tonic, blood purifier, pain reliever, as well as a treatment for skin ailments, and gastric complaints. It has also been used to heal wounds and prevent infections. Chaga has often been referred to in Asian culture as a ‘Gift from God,’ the ‘King of Herbs,’ and the ‘Mushroom of Immortality.’ Chaga was introduced to the western world by the famous Russian Nobel Laureate Alexander Solzhenitsyn in his famous novel ‘The Cancer Ward,’ published in 1968, which is a semi-autobiographical book about his being treated for cancer in a Siberian hospital. In it, he mentioned how impressed he was with the healing powers of chaga, including giving it much of the credit for his recovery.

Wild crafted (grows naturally in the wild) Siberian Chaga Extract from Chaga International is by far the best chaga on the market that I am aware of. The extraction process, which was developed in 2003 by James Osugi, an American scientist living in Asia, uses low pressure and low-temperature water. The best chaga comes from Siberia, which has the harshest winters (necessitating this chaga to develop superior defense mechanisms) and comes in different grades. Chaga International uses only the best grade (top 2 to 3%) Siberian chaga. It is blended with a proprietary mineral water called Pi Water, which facilitates quick absorption into the bloodstream and cells.  It is water soluble, almost tasteless and odorless. Healthy people only need about 20 drops daily to keep their bodies in balance. People with health challenges usually notice change more quickly and should work up to 40 or more drops daily. When the body is in balance, disease cannot manifest itself. Our Chaga Extract contains only mineral water and chaga (no preservatives), has a long shelf life and requires no refrigeration. So far, no allergic reactions have been reported, even among those allergic to mushrooms.  

Many chaga products have come on the market since James Osugi introduced his in 2003. Most are in the forms of capsules, powders, teas, and tinctures, which used solvents to extract it. None of them that we have found remotely comes close to our Chaga. I sent samples to several dowsers who all found it to be one the most (if not the most) powerful nutritional products they have ever tested.

Of the 215 known nutrients in chaga, some of the most important are: SOD (Super Oxide Dismutase)—a superior antioxidant that keeps cell membranes supple and healthy; Beta Glucans / Polysaccharides—a class of carbohydrates that stimulates the body's defense mechanisms, found to have anti-tumor, anti-bacterial, and anti-viral properties - includes the 8 polysaccharides that are needed for cells to communicate with each other; Betulinic Acid—a powerful immune enhancer with anti-tumor, anti-bacterial, anti-viral, anti-malarial and anti-inflammatory properties;  Melanin—a pigment that stimulates DNA repair and promotes healthy skin, hair and eyes and has anti-inflammatory and anti-tumor properties; Polyphenols—superior antioxidants, including DBL, which increases apoptosis (programmed cancerous cell death) and suppresses the invasion of cancerous cells; Germanium—helps cleanse blood, normalize blood pressure and prevent tumors; and Triterpenes—organic compounds that help with digestion, the liver, respiratory ailments and balancing cholesterol - includes Inotodiol, which has been found to have significant anti-tumor, anti-viral, and anti-fungal (possibly making chaga the only anti-fungal fungus) activity. These active ingredients work synergistically (in other words, 1+1 does not =2 but 1+1=3 or more).

Chaga is an adaptogen, which helps relieve stress and supports the immune, hormonal, and nervous systems. It has been shown to increase human Natural Killer (NK) cell activity by up to 300%. It helps balance blood sugar and is a powerful detoxifier, anti-candida, anti-inflammatory (recent studies show that it may help with arthritis, atherosclerosis and digestive-tract inflammatory conditions), as well as protects against radiation, including the radiation we get from electricity, plasma TV’s, cell phones, X-rays, CT scans, flying at high altitudes, etc.

Siberian Chaga has been endorsed by Dr. Alicia Alvarez, founder of the Women and Cancer Fund based in Chandler, Arizona, who along with James Osugi conducted major studies on Indian Reservations in the US. The Annie Appleseed Project for breast cancer has also endorsed Chaga. In addition to helping conditions that people have traditionally used it for, testimonials from people using chaga report it helping with such conditions as diabetes, high cholesterol, high blood pressure, depression, insomnia, IBS, CFS, HIV/AIDS, colds, flues, herpes, kidney and bladder problems, arthritis, bronchitis, allergies, and skin problems. According to Karl Maret, M.D., a renowned expert on energetic medicine, a major cause of disease is blockages in the body's electrical grid mainly due to such things as cell phones, cell phone towers, microwaves, and heavy metals found in many of the foods (even organic) we eat today, which causes 'short-circuiting' to occur in our bodies. Our Chaga Extract helps to reestablish the electrical grid, allowing the body to help heal itself and function correctly. Leading acupuncturists testing Chaga have seen all acupuncture points being stimulated shortly after taking Chaga. Taking our Chaga is like having 'Herbal Acupuncture.' To quote Dr. Frank Chaviano, a member of the Presidential Health Task Force, "Chaga is as close to the Magic Bullet as you are going to get!"

I first came across this Chaga in 2005, but never realized what a great product it was until last September when I ran out after taking it regularly for 3 or 4 months. After a few days without it, I was looking for any drops left in my empty bottles. It is the first thing I take every morning and the last thing I take every night. If I had to choose only one product that I would take for the rest of my life, Chaga would be my choice. At 62, I still feel like I am still in my 20’s. There is nothing I could do in my youth that I feel I could not do today and in some cases maybe even better. This winter, after shoveling our 400-foot driveway with up to a foot of snow several times, I have yet to get tired or have sore muscles afterward. I feel that Chaga will allow me to feel this way for many years to come.   – 25 year Health Enthusiast and Marketer of Health Supplements



Chaga Research

For the past forty (40) years 1,600 modern scientific studies have demonstrated and proven the pharmacological effects for the immune, hormonal and central nervous system. Siberian Chaga is neither a plant nor animal yet its DNA make up is thirty (30%) per cent closer to humans than plants. Classified scientifically as: Basidiomycetes mushrooms to which there are approximately 200 species have demonstrated medicinal values. Siberian Chaga is far and above any other Basidiomycetes. Siberian Chaga contains the highest value ever recorded in the ORAC Scale and is over 40,000 times more potent in antioxidants than the closest natural product in foods or essential oils.

Siberian Chaga Studies Include:

1. Cancer research: a) breast, b) lung, c) stomach d) melanoma and e) bone.

2. Leukemia

3. HIV and Immune Compromised diseases

4. Diabetes

5. Ulcers

6. Cardiovascular Diseases

7. Pneumonia and Lung Disorders

Chaga has been researched as an antiviral, anti-tumor for breast and uterine and other cancers, diabetes, Immunity/Longevity (increasing vital force and strengthen the immune system), as an immune Amphoteric, for reducing the blood pressure, and slowing down heart rate.

Chronic bronchitis or any other infection is a sign of weakened immune systems.

Research papars:

Kahlos K, Kangas L, Hiltunen R. Antitumor activity of some compounds and fractions from an n-hexane extract of Inonotus obliquus in vitro Acta Pharm Fennica 1987; 96: 33–40

Burczyk J, Gawron A, Slotwinska M, Smietana B, Terminska K. Antimitotic activity of aqueous extracts of Inonotus obliquus Boll Chim Farm 1996; 135: 306–9[Medline]

Babitskaya VG, Scherba VV, Ikonnikova NV, Bisko NA, Mitropolskaya NY. Melanin complex from medicinal mushroom Inonotus obliquus (Pers.:Fr.) Pilat (Chaga) (Aphyllophoromycetidae) Int J Med Mushrooms 2002; 4: 139–45

The following pages contain research and studies pertaining specifically to and in the following order:

o   Anti- Cancer effects of Chaga preparation

o   Anti-Cancer effects invitro and invivo

o   Chaga mushroom treatment affords cellular protection against endogenous DNA damage

o   Inonotus obliquus has the capacity to scavenge free radicals and can protect cells against oxidative stress

o   Anti-oxidant effect

o   Anti-Cancer effect as an immune system modifier

o   Anti-inflammatory and anti-nociceptive effects in gastrointestinal cancer, diabetes and cardiovascular disease

o   Liver cancer

o   Tumor Necrosis, enhance apoptosis (tumor cell death) and inhibit invasion

o   Anti-Tumor promoting activity

o   Intercellular Communication

o   Diabetes – significant decrease in blood glucose level

This represents a handful of reports and studies one can find with ease when researching the benefits of Chaga as relating to specific diseases. Please take time and review the many more available on and and other outlets. Even more enlightenment and information is found as you research the individual components in chaga as listed in this review.


Genoprotective effects AND development of anti-cancer preparations

Melanin Complex from Medicinal Mushroom Inonotus obliquus (Pers.: Fr.) Pilat (Chaga) (Aphyllophoromycetideae)

Nina A. Bisko

M. G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine

Nadezda Yu. Mitropolskaya

M. G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine, Tereschenkivska Str. 2, Kiev, 252601, Ukraine

Natalia V. Ikonnikova

Institute of Microbiology of the National Academy of Sciences of Byelorussia, 2 Kuprevich Str., Minsk 220141, Belarus


The production of melanin complex of Inonotus obliquus (Pers.: Fr.) Pilat (Chaga in Russian) in submerged conditions was studied. It was demonstrated that copper ions (0.008%), pyrocatechol (1.0 mM), and tyrosine (20.0 mM) stimulated this process. It has been estimated that melanin of I. obliquus has antioxidant and genoprotective effects. The investigation of the element composition of the pigment shows that it contains 38.2% C, 5.54% H, and trace amounts of N. The pigment was characterized by the following properties: the extinction coefficient E 0.001% (l = 465 nm) = 0.02; content of COOH groups = 0.93%, CO groups = 1.05%, OCH3 groups = 0.96%, total OH groups 16.9% including aliphatic groups 15.65% and phenolic groups 1.25%. The data obtained in our work demonstrate high antioxidant and genoprotective effects of I. obliquus melanin on peroxidasecatalyzed oxidation of aminodiphenyls. These properties of melanin of I. obliquus may be used for the development of anticarcinogenic preparations.

Complete Article can be bought for $35 at:,3ff76b291e5f4359,4000bb317b94495e.html

Anti-cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus.

Life Sci.  2006; 79(1):72-80 (ISSN: 0024-3205)

Kim YO ; Park HW ; Kim JH ; Lee JY ; Moon SH ; Shin CS

Department of Biotechnology, College of Engineering, Yonsei University, Shinchon-dong, Seodaemoon-gu, Seoul 120-749, South Korea.

The endo-polysaccharide extracted from mycelia of Inonotus obliquus (Pers.:Fr.) Pil. (Hymenochaetaceae) is a specific activator of B cells and macrophages. However, the in vivo anti-cancer effects and the chemical structure of the endo-polysaccharide are unknown. We purified the endo-polysaccharide, investigated its anti-cancer effects via in vitro and in vivo assays, and performed a structural characterization. The endo-polysaccharide was extracted from I. obliquus mycelia cultivated in a 300-l pilot fermenter, followed by hot water extraction and ethanol precipitation. Purification was achieved by DEAE-cellulose ion-exchange chromatography and gel-permeation chromatography. Chemical analysis revealed that the purified endo-polysaccharide is an alpha-linked fucoglucomannan with a molecular weight of approximately 1,000 kDa. The anti-cancer activities of the endo-polysaccharide against various types of tumor cells were determined. No direct toxicity against either cancer or normal cells was observed. Intraperitoneal administration of the endo-polysaccharide significantly prolonged the survival rate of B16F10-implanted mice, resulting in a 4.07-fold increase in the survival rate at a dose of 30 mg/kg/day. After 60 days of feeding, approximately 67% of the initial number of mice survived with no tumor incidence based on macroscopic examination. These results indicate that the anti-cancer effect of endo-polysaccharide is not directly tumorcidal but rather is immuno-stimulating.•        PreMedline Identifier: 16458328

Chaga mushroom extract inhibits oxidative DNA damage in human lymphocytes as assessed by comet assay.  Park YK, Lee HB, Jeon EJ, Jung HS, Kang MH.

Department of Medical Nutrition, Kyunghee University, 1 Hoekidong, Dongdaemoonku, Seoul 130-701, South Korea.

The Chaga mushroom (Inonotus obliquus) is claimed to have beneficial properties for human health, such as anti-bacterial, anti-allergic, anti-inflammatory and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protection of cell components against free radicals.

We evaluated the effect of aqueous Chaga mushroom extracts for their potential for protecting against oxidative damage to DNA in human lymphocytes. Cells were pretreated with various concentrations (10, 50, 100 and 500 microg/mL) of the extract for 1 h at 37 degrees C. Cells were then treated with 100 microM of H2O2 (Hydrogen Peroxide) for 5 min as an oxidative stress. Evaluation of oxidative damage was performed using single-cell gel electrophoresis for DNA fragmentation (Comet assay). Using image analysis, the degree of DNA damage was evaluated as the DNA tail moment.Cells pretreated with Chaga extract showed over 40% reduction in DNA fragmentation compared with the positive control (100 micromol H2O2 treatment). Thus, Chaga mushroom treatment affords cellular protection against endogenous DNA damage.

Antioxidant effect of Inonotus obliquus  J Ethnopharmacol.  2005; 96(1-2):79-85 (ISSN: 0378-8741)

Cui Y ; Kim DS ; Park KC Department of Dermatology, Seoul National University, Bundang Hospital, 300 Gumi-Dong, Bundang-Gu, Seongnam-Si, Kyoungki-Do 463-707, Republic of Korea.

The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been widely used as a folk medicine in Russia, Poland and most of the Baltic countries. The purpose of this study was to elucidate the antioxidant capacities of Inonotus obliquus. Four extracts from the fungus were evaluated for antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide, and peroxyl radicals. The polyphenolic extract had a strong antioxidant activity, and the extract containing triterpenoids and steroids presented a relatively strong antioxidant effect. The polysaccharide extract, however, was inactive. The protective effects of these four extracts were assessed against hydrogen peroxide-induced oxidative stress using a human keratinocyte cell line, HaCaT. Our results show that the polyphenolic extract protected these cells against hydrogen peroxide-induced oxidative stress, while the polysaccharide, triterpenoid and steroid extracts were ineffective. Additionally, the remnant polyphenolic and low molecular weight polysaccharide extracts showed a weakly protective effect at a concentration of 50 microg/ml. Our results indicate that Inonotus obliquus has the capacity to scavenge free radicals at concentrations higher than 5 microg/ml and that the polyphenolic extract can protect cells against oxidative stress.•        PreMedline Identifier: 15588653

Immuno-stimulating effect of the endo-polysaccharide produced by submerged culture of Inonotus obliquus.  Life Sci.  2005; 77(19):2438-56 (ISSN: 0024-3205)

Kim YO ; Han SB ; Lee HW ; Ahn HJ ; Yoon YD ; Jung JK ; Kim HM ; Shin CS

Department of Biotechnology, College of Engineering, Yonsei University, Shinchon-dong, Seodaemoon-gu, Seoul 120-749, South Korea.

Inonotus obliquus BELYU1102 was selected from 12 different strains of Inonotus as a producer of immuno-stimulating polysaccharide. After a batch fermentation of I. obliquus BELYU1102 was carried out in a 300 l pilot vessel, endo-polysaccharide and exo-polysaccharide were both obtained. The proliferation activity of endo-polysaccharide for splenic cells was much higher than the activity of exo-polysaccharide. The active endo-polysaccharide was produced primarily during the late stationary phase. Enhanced proliferation and polyclonal IgM antibody production were observed in B cells by purified water-soluble endo-polysaccharide. Nitrite production and expression of IL-1beta, IL-6, TNF-alpha, and iNOS in macrophages were also enhanced. However, the endo-polysaccharide did not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the IL-4 expression of Th2 cells. The endo-polysaccharide showed activities similar to lipopolysaccharide (LPS) for B cells and macrophages, but there was a large difference between the two polysaccharides because cellular activations induced by endo-polysaccharide were not affected by polymyxin B, a specific inhibitor of LPS. The endo-polysaccharide appeared to have other cellular binding sites with TLR-4 and did not show a direct toxicity against tumor cells. However, indirect anti-cancer effects via immuno-stimulation were observed. The mycelial endo-polysaccharide of I. obliquus is a candidate for use as an immune response modifier. Submerged mycelial cultures are advantageous for industrial production of polysaccharides.

•          PreMedline Identifier: 15970296

In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus.

J Ethnopharmacol.  2005; 101(1-3):120-8 (ISSN: 0378-8741)

Park YM ; Won JH ; Kim YH ; Choi JW ; Park HJ ; Lee KT

Department of Biochemistry, College of Pharmacy, Kyung-Hee University, Dongdaemun-Ku, Hoegi-Dong, Seoul 130-701, South Korea.

The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been traditionally used for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes in Russia, Poland and most of Baltic countries. This study was designed to investigate the anti-inflammatory and anti-nociceptive effects of the methanol extract from Inonotus obliquus (MEIO) in vivo and in vitro. MEIO (100 or 200 mg/(kgday), p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activity, as determined by an acetic acid-induced abdominal constriction test and a hot plate test in mice. To reveal the mechanism of the anti-inflammatory effect of MEIO, we examined its effect on lipopolysaccharide (LPS)-induced responses in a murine macrophage cell line RAW 264.7. MEIO was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, MEIO potently inhibited the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, MEIO inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), and this was associated with the prevention of inhibitor kappaB degradation and a reduction in nuclear p65 protein levels. Taken together, our data indicate that the anti-inflammatory and anti-nociceptive properties of MEIO may be due to the inhibition of iNOS and COX-2 expression via the down-regulation of NF-kappaB binding activity.

•          PreMedline Identifier: 15905055

Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells. Youn MJ, Kim JK, Park SY, Kim Y, Kim SJ, Lee JS, Chai KY, Kim HJ, Cui MX, So HS, Kim KY, Park R.Vestibulocochlear Research Center, Wonkwang University School of Medicine, #344-2, Shinyoung-dong, Iksan, Jeonbuk 570-749, Korea.

AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines, HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, flow cytometry analysis, Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells, as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner, which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition, G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53, pRb, p27, cyclins D1, D2, E, cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma.

PMID: 18203281 [PubMed - indexed for MEDLINE]

Identification of a novel blocker of IkappaBalpha kinase activation that enhances apoptosis and inhibits proliferation and invasion by suppressing nuclear factor-kappaB.

Sung B, Pandey MK, Nakajima Y, Nishida H, Konishi T, Chaturvedi MM, Aggarwal BB.

Cytokine Research Section, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Unit 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

3,4-dihydroxybenzalacetone (DBL) is a polyphenol derived from the medicinal plant Chaga [Inonotus obliquus (persoon) Pilat]. Although Chaga is used in Russia folk medicine to treat tumors, very little is known about its mechanism of action. Because most genes involved in inflammation, antiapoptosis, and cell proliferation are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we postulated that DBL activity is mediated via modulation of the NF-kappaB activation pathway. We investigated the effects of DBL on NF-kappaB activation by electrophoretic mobility shift assay and on NF-kappaB-regulated gene expression by Western blot analysis. We found that DBL suppressed NF-kappaB activation by a wide variety of inflammatory agents, including tumor necrosis factor (TNF), interleukin-1beta, epidermal growth factor, okadaic acid, phorbol 12-myristate 13-acetate, and lipopolysaccharide. The suppression was not cell type specific and inhibited both inducible and constitutive NF-kappaB activation. DBL did not interfere with the binding of NF-kappaB to DNA but rather inhibited IkappaBalpha kinase activity, IkappaBalpha phosphorylation and degradation, p65 phosphorylation, and translocation. DBL also suppressed the expression of TNF-induced and NF-kappaB-regulated proliferative, antiapoptotic, and metastatic gene products. These effects correlated with enhancement of TNF-induced apoptosis and suppression of TNF-induced invasion. Together, our results indicate that DBL inhibits NF-kappaB activation and NF-kappaB-regulated gene expression, which may explain the ability of DBL to enhance apoptosis and inhibit invasion. PMID: 18202022 [PubMed - indexed for MEDLINE]

Structure determination of inonotsuoxides A and B and in vivo anti-tumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus.

Nakata T, Yamada T, Taji S, Ohishi H, Wada S, Tokuda H, Sakuma K, Tanaka R.

Department of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Two new lanostane-type triterpenoids, inonotsuoxides A (1) and B (2) along with three known lanostane-type triterpenoids, inotodiol (3), trametenolic acid (4), and lanosterol (5), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanakake) (Russian name: Chaga). Their structures were determined to be 22R,25-epoxylanost-8-ene-3beta,24S-diol (1) and 22S,25-epoxylanost-8-ene-3beta,24S-diol (2) on the basis of spectral data including single crystal X-ray analysis. These compounds except for 2 were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. The most abundant triterpene, inotodiol (3), was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compound 3 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.

PMID: 17049251 [PubMed - indexed for MEDLINE]

Reversal of the TPA-induced inhibition of gap junctional intercellular communication by Chaga mushroom (Inonotus obliquus) extracts: effects on MAP kinases.

Park JR, Park JS, Jo EH, Hwang JW, Kim SJ, Ra JC, Aruoma OI, Lee YS, Kang KS.

Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine and BK 21 Program for Veterinary Science, Seoul National University, Sillim 9-dong, Gwanak-gu, Seoul 151-742, South Korea.

Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase. PMID: 17012771 [PubMed - indexed for MEDLINE]

Antihyperglycemic and antilipidperoxidative effects of dry matter of culture broth of Inonotus obliquus in submerged culture on normal and alloxan-diabetes mice.

Sun JE, Ao ZH, Lu ZM, Xu HY, Zhang XM, Dou WF, Xu ZH.

Lab of Pharmaceutical Engineering, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, PR China.

AIM OF THE STUDY: The antihyperglycemic and antilipidperoxidative effects of the dry matter of culture broth (DMCB) of Inonotus obliquus were investigated. MATERIALS AND METHODS: The normal, glucose-induced hyperglycemic and alloxan-induced diabetic mice were used to evaluate the antihyperglycemic and antilipidperoxidative effects of the DMCB of Inonotus obliquus. RESULTS: Treatment with the DMCB (500 and 1000 mg/kg body weight) exhibited a mild hypoglycemic effect in normal mice, and failed to reduce the peak glucose levels after glucose administration. However, euglycemia was achieved in the DMCB of Inonotus obliquus (1000 mg/kg) and glibenclamide-treated mice after 120 min of glucose loading. In alloxan-induced diabetic mice, the DMCB (500 and 1000 mg/kg body weight for 21 days) showed a significant decrease in blood glucose level, the percentages reduction on the 7th day were 11.90 and 15.79%, respectively. However, feeding of this drug for 3 weeks produced reduction was 30.07 and 31.30%. Furthermore, the DMCB treatment significantly decreased serum contents of free fatty acid (FFA), total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C), whereas effectively increased high density lipoprotein-cholesterol (HDL-C), insulin level and hepatic glycogen contents in liver on diabetic mice. Besides, the DMCB treatment significantly increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities except for decreasing maleic dialdehyde (MDA) level in diabetic mice. Histological morphology examination showed that the DMCB restored the damage of pancreas tissues in mice with diabetes mellitus. CONCLUSIONS: The results showed that the DMCB of Inonotus obliquus possesses significant antihyperglycemic, antilipidperoxidative and antioxidant effects in alloxan-induced diabetic mice.

PMID: 18434051 [PubMed - in process]

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