Russian Spam, Betulinic Acid and Chaga Mushrooms
Jacob Schor, ND
September 5, 2007
Russian email spam inundates my inbox daily. I cannot read Russian so have no clue what they are selling. I can guess. It started a year ago when I was searching for a source of Chaga mushrooms. Our infamous Santa Claus Newsletter from December 2005 talked about these mushrooms. The native people of Siberia consider these mushrooms as a specific treatment for melanoma. Researchers at the University of Chicago are investigating betulinic acid derived from birch bark as a treatment for melanoma. Chaga mushrooms grow on birch trees and convert the betulin in the bark into betulinic acid.
The original Santa newsletter: http://denvernaturopathic.com/news/santaandbetulinic.html
We could not find a decent source for Chaga mushrooms. The Russian sites I found selling the mushroom could not guarantee the quality of their products the way I am accustomed to. The Russian spam did not build confidence in doing business with these sites either. JHS Naturals, a company we have done business with for many years, has recently added Chaga to their line of mushrooms extracts. They have been working on this for several years and have finally found a reliable source that supplies them with wild crafted Chaga mushrooms from Siberia .
A quick rummage through the National Library of medicine turns up several new papers on betulinic acid published since the Santa newsletter. One written by researchers from Dartmouth and published just this July details attempts at fiddling with betulinic acid and modifying its chemical structure slightly to make it more potent against cancer cells. [i] Of course, these modifications make it patentable.
Another paper from researchers in Poland was published in October 2006 and began to detail the chemical mechanisms by which betulinic acid works. Adding betulinic acid to cancer cells decreases their expression of bcl-2 and cyclin D1, which some of our readers will understand, but don't feel bad if you don't say, “cool” out loud. The bottom line is that decreasing production of these unpronounceable things, “inhibits proliferation, migration and induces apoptosis in cancer cells.” Or in simple language, prevents cancer cells from growing, spreading and convinces them to kill themselves.
Up to this study we thought of betulinic acid only in terms of skin cancer but these researchers tested it on a host of cancer cell types and found it useful:
If, like me, your college biology course didn't mention bcl-2 expression, you can read and appreciate this list of cancer types.
Looking more carefully, there is a Dutch study published in Cancer Letters this past June which found betulinic acid useful in a variety of cancer types.
Betulinic acid can be made from birch bark by fermentation. There's a company up in Duluth , Minnesota that has figured out how to do this with scrap bark left over from lumber mills. [iv] Though they can apparently produce betulinic acid in sizable quantities, they are not willing to sell it, at least to people like us or supplement companies. They are apparently restricted to only selling it for medical research.
The Chinese have also figured out a way to make betulinic acid [v] and will sell it to us if we purchase several hundred kilos at a time. A number of other interesting reviews and studies have been published, that I will not bother to list. [vi] [vii] [they will be on the website version of this article]
There is an interesting paper on actinic keratosis. Using a birch bark topical ointment cleared lesions in 79% of the study participants. [viii]
You can purchase small quantities of betulinic acid for topical use at a website that sells ingredients for ‘make it yourself' skin care lotions. This notion reminds me of the “Do-It-Ur-Self Plumbing” store that I have been forced to frequent some weekends. The skin lotion website, not the plumbing one, is: http://skinactives.com/
Chaga mushrooms contain betulinic acid plus a variety of closely related chemicals and may prove to be a better method of obtaining betulinic acid than the fermented waste products of lumber mills. Currently, commercial interests are focused on finding anticancer drugs that you can manufacture in quantity not some exotic mushroom that has to be gathered in Siberia . Yet we do find some researchers investigating Chaga for cancer treatment. [ix]
Until betulinic acid becomes available in quantity, we do have Chaga mushrooms, which just might work better than the pure acid.
You can read all about all sorts of medicinal mushrooms at JHS Naturals' website at:
You can purchase all sorts of mushrooms online from JHS, but if you buy their products through us, we can usually save you a little money, so call us first.
Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities.
Dartmouth Medical School , Hanover , NH 03755 , USA .
Betulinic acid (BA), a pentacyclic triterpene isolated from birch bark and other plants, selectively inhibits the growth of human cancer cell lines. However, the poor potency of BA hinders its clinical development, despite a lack of toxicity in animal studies even at high concentrations. Here, we describe six BA derivatives that are markedly more potent than BA for inhibiting inducible nitric oxide synthase, activating phase 2 cytoprotective enzymes, and inducing apoptosis in cancer cells and in Bax/Bak(-/-) fibroblasts, which lack two key proteins involved in the intrinsic, mitochondrial-dependent apoptotic pathway. Notably, adding a cyano-enone functionality in the A ring of BA enhanced its cytoprotective properties, but replacing the cyano group with a methoxycarbonyl strikingly increased potency in the apoptosis assays. Higher plasma and tissue levels were obtained with the new BA analogues, especially CBA-Im [1-(2-cyano-3-oxolupa-1,20(29)-dien-28-oyl)imidazole], compared with BA itself and at concentrations that were active in vitro. These results suggest that BA is a useful platform for drug development, and the enhanced potency and varied biological activities of CBA-Im make it a promising candidate for further chemoprevention or chemotherapeutic studies.
PMID: 17620440 [PubMed - in process]
Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells.
Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University , Akademicka 19, 20-033, Lublin , Poland . firstname.lastname@example.org
Betulinic acid (BA) is a pentacyclic triterpene found in many plant species, among others in the bark of white birch Betula alba. BA was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial and anti-inflammatory activities, and in particular to inhibit growth of cancer cells. The aim of the study was further in vitro characterization of BA anticancer activity. In this study, we demonstrated a remarkable antiproliferative effect of BA in all tested tumor cell cultures including neuroblastoma, rabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukemia and multiple myeloma, as well as in primary cultures isolated from ovarian carcinoma, cervical carcinoma and glioblastoma multiforme. Furthermore, we have shown that BA decreased cancer cell motility and induced apoptotic cell death. We also observed decrease of bcl2 and cyclin D1 genes expression, and increase of bax gene expression after betulinic acid treatment. These findings demonstrate the anticancer potential of betulinic acid and suggest that it may be taken into account as a supportive agent in the treatment of cancers with different tissue origin.
PMID: 16964520 [PubMed - indexed for MEDLINE]
Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types.
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Betulinic acid (BA) is a widely available plant-derived triterpene with reported activity against cancer cells of neuroectodermal origin and leukaemias. Treatment with BA was shown to protect mice against transplanted human melanoma and led to tumor regression. In contrast, cells from healthy tissues were resistant to BA and toxic side-effects in animals were absent. These findings have raised interest in the chemotherapeutical anti-cancer potential of BA. A comprehensive assessment of the efficacy of BA against the clinically most important cancer types is currently lacking. Therefore, we tested the in vitro sensitivity of broad cell line panels derived from lung, colorectal, breast, prostate and cervical cancer, which are the prevalent cancer types characterized with highest mortalities in woman and men. Multiple assays were used in order to allow a reliable assessment of anti-cancer efficacy of BA. After 48 h of treatment with BA, cell viability as assessed with MTT and cell death as measured with propidium iodide exclusion showed clear differences in sensitivity between cell lines. However, in all cell lines tested colony formation was completely halted at remarkably equal BA concentrations that are likely attainable in vivo. Our results substantiate the possible application of BA as a chemotherapeutic agent for the most prevalent human cancer types.
PMID: 17169485 [PubMed
Simultaneous determination of betulin and betulinic acid in white birch bark using RP-HPLC.
Zhao G ,
Yan W ,
Cao D .
Department of Chemistry, Zhejiang University , Hangzhou 310027, PR China.
A simple procedure is described for the simultaneous extraction and determination of betulin and betulinic acid in white birch bark. The extraction was checked using different solvents: dichloromethane, ethyl acetate, acetone, chloroform, methanol and 95% ethanol (aqueous solution, v/v). It was found 95% ethanol was a good extraction solvent that allowed extraction of triterpenoid with a highest content. Separation was achieved on a reversed phase C(18) column with acetonitrile-water 86:14 (v/v). Detection was accomplished with UV detection at lambda=210nm. Using this method, the bioactive triterpenoid in white birch bark were simultaneously determined. Significant variations in the content of betulin and betulinic acid in white birch bark growing in different locations of China were also observed.
PMID: 17084057 [PubMed - as supplied by publisher]
Pharmacological properties of the ubiquitous natural product betulin.
Alakurtti S ,
Makela T ,
Koskimies S ,
Yli-Kauhaluoma J .
Faculty of Pharmacy, Division of Pharmaceutical Chemistry, University of Helsinki , Helsinki , Finland .
Betulin (lup-20(29)-ene-3beta,28-diol) is an abundant naturally occurring triterpene and it is found predominantly in bushes and trees forming the principal extractive (up to 30% of dry weight) of the bark of birch trees . Presently, there is no significant use for this easily isolable compound, which makes it a potentially important raw material for polymers and a precursor of biologically active compounds. Betulin can be easily converted to betulinic acid, which possesses a wide spectrum of biological and pharmacological activities. Betulinic acid has antimalarial and anti-inflammatory activities. Betulinic acid and its derivatives have especially shown anti-HIV activity and cytotoxicity against a variety of tumor cell lines comparable to some clinically used drugs . A new mechanism of action has been confirmed for some of the most promising anti-HIV derivatives, which makes them potentially useful additives to the current anti-HIV therapy. Betulinic acid is specifically cytotoxic to several tumor cell lines by inducing apoptosis in cells. Moreover, it is non-toxic up to 500 mg/kg body weight in mice. The literature concerning derivatization of betulin for structure-activity relationship (SAR) studies and its pharmacological properties is reviewed.
PMID: 16716572 [PubMed - indexed for MEDLINE]
Betulinic acid derivatives as anticancer agents: structure activity relationship.
Mukherjee R ,
Kumar V ,
Srivastava SK ,
Agarwal SK ,
Burman AC .
Medicinal Chemistry, Dabur Research Foundation, 22 Site IV, Sahibabad, Ghaziabad 201010, UP, India .
Betulinic acid, a pentacyclic triterpene, is widely distributed throughout the tropics. It possesses several biological properties such as anticancer, anti-inflammatory, antiviral, antiseptic, antimalarial, spermicidal, antimicrobial, antileshmanial, antihelmentic and antifeedent activities. However, betulinic acid was highly regarded for its anticancer and anti-HIV activities. Anticancer role of betulinic acid appeared by inducing apoptosis in cells irrespective of their p53 status. Due to high order safety in betulinic acid, a number of structural modifications carried out to improve its potency and efficacy. The C-1, C-2, C-3, C-4, C-20 and C-28 positions are the diversity centers in betulinic acid, and the derivatives resulted on various structural modifications at these positions screened for their anticancer activity. This review presents the structure activity relationship carried out on C-1, C-2, C-3, C-4, C-20, C-28, A-ring, D-ring and E-ring modified betulinic acid derivatives. We have compiled the most active betulinic acid derivatives along with their activity profile in each series. Structure activity relationship studies revealed that C-28 carboxylic acid was essential for the cytotoxicity. The halo substituent at C-2 position in betulinic acid enhanced the cytotoxicity. Though the relation of the cytotoxicity with the nature of substituents at C-3 position could not be generalized but the ester functionality appeared to be a better substituent for enhancing the cytotoxicity. An interesting observation is that the three rings skeleton (A, B and C rings) had played an important role in eliciting anticancer activity, which could be a new molecular skeleton to design new anticancer drugs.
PMID: 16712455 [PubMed - indexed for MEDLINE]
[Treatment of actinic keratoses with birch bark extract: a pilot study]
[Article in German]
Huyke C ,
Laszczyk M ,
Scheffler A ,
Ernst R ,
Schempp CM .
Universitats-Hautklinik, Hauptstr. 7, D-79104 Freiburg .
BACKGROUND: Birch bark contains a variety of apoptosis-inducing and anti-inflammatory substances such as betulinic acid, betulin, oleanolic acid and lupeol. Therefore, birch bark extract may be effective in the treatment of actinic keratoses. To address this issue, a pilot study using a standardized birch bark ointment was performed. METHODS: Twenty-eight patients with actinic keratoses were enrolled in this prospective, non-randomized pilot study. Fourteen patients were treated with birch bark ointment only; fourteen patients received a combination therapy with cryotherapy and birch bark ointment. Treatment response was assessed clinically after two months. RESULTS: Clearing of more than 75 % of the lesions was seen in 79 % of the patients treated with birch bark ointment monotherapy. The response rate of the combined treatment modality was 93 %. Therapy with birch bark ointment was well tolerated. CONCLUSION: In this pilot study, a standardized birch bark extract was effective in the treatment of actinic keratoses. This therapy is easy to perform and it has no side effects. Birch bark ointment may be a new therapeutic option for actinic keratoses.
PMID: 16503940 [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.
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]