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Cosmeceutical Critique: Mushrooms: Part II
 

There are 14,000 known species of mushrooms, and many have been used as food and folk medicines for thousands of years. About 200 species have been used for medical purposes in countries ranging from China, Japan, Korea, and Russia to Canada and the United States (Appl. Microbiol. Biotechnol. 2002;60:258–74; Crit. Rev. Immunol. 1999;19:65–96).


By far, the most extensive use of mushrooms for medical purposes has been in China, Japan, and Korea to treat allergies, arthritis, bronchitis, and scleroderma as well as cancer, especially of the stomach, esophagus, and lungs. The mushrooms used in traditional medicine include Lentinus edodes (shiitake), Ganoderma lucidum (lingzhi in Chinese, reishi in Japanese), Cordyceps sinensis, Grifola frondosa (maitake), Hericium erinaceum (yamabushitake), Inonotus obliquus (chaga), Schizophyllum commune, Trametes versicolor, and Flammulina velutipes (Life. Sci. 2004;75:1051–62; Integr. Cancer Ther. 2003;2:358–64; Mini. Rev. Med. Chem. 2004;4:873–9; Crit. Rev. Immunol. 1999;19:65–96).


Mushrooms contain compounds believed to have significant biologic activity, including triterpenes, proteins, lipids, cerebrosides, phenols, vitamins, fiber, and amino acids. They also have been found to possess a high content of biologically active polysaccharides with demonstrated antitumor and immuostimulating properties (Mini Rev. Med. Chem. 2004;4:873–9; Appl. Microbiol. Biotechnol. 2002;60:258–74).


In this second column on mushrooms, which follows the June column on the heavily researched species Ganoderma lucidum, I focus on some of the mushrooms used in newer dermatologic products.


L. edodes


The ethanol-soluble extract of L. edodes has been shown to reduce the proliferation of murine skin carcinoma cells (CH72), and to dose- and time-dependently induce apoptosis in these cells. Extracts of other mushrooms (Grifola frondosa, Ganoderma lucidum, and H. erinaceum) have been shown to have only a negligible effect on cancer cells (Cancer Lett. 2005;220:21–8).


In a different study, an ethyl acetate fraction of L. edodes was observed to exert concentration-dependent antiproliferative effects on several cell lines, when tested using the MTT assay (MTT is 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The antiproliferative effects were seen in all of the cell lines tested, including human breast carcinoma (MCF-7 and MDA-MB-453), human nonmalignant breast epithelial cells (MCF-10F), and myeloma (IM-9 and RPMI-8226). The researchers concluded apoptosis induced by the active ingredients in shiitake mushrooms—the so-called mycochemicals—might cause the growth inhibition in tumor cells (J. Altern. Complement. Med. 2006;12:125–32).


Two ?-glucan constituents of L. edodes, lentinan and micellapist, are sold in Japan as a medicine and a food supplement, respectively. In a study of mushroom polysaccharides, lentinan exhibited antitumor and immunomodulating activity through immunocyte cytokine production (Gan To Kagaku Ryoho 2006;33:1726–9; Carbohydr. Res. 2005;340:1515–21; Int. J. Immunopharmacol. 1995;17:465–74; Biofactors 2004;21:407–9). In a recent study, investigators evaluated the antitumor activities of lentinan in B10.D2 mice implanted with S908D2 tumor cells. They found tumor growth was suppressed in animals treated with lentinan, that tumor-bearing mice treated with lentinan survived longer than did untreated mice, and that tumor cytotoxicity in the lentinan-treated group was reduced by a treatment of splenocytes with anti-CD8 antibody (Gan To Kagaku Ryoho 2006;33:1726–9).


To ascertain whether lentinan extracted from shiitake mushrooms could maintain its antitumor capacity through oral administration, as opposed to the more common parenteral administration, researchers tested lentinan using murine lymphoma (K36) cells in an AKR mouse model. Subsequently, they tested the compound in mice inoculated with human colon carcinoma cell lines. In both types of mice, the tumors regressed in animals that had been fed lentinan 7 days before inoculation with the cancer cells, compared with control mice that were not fed lentinan.


In the same study, lymphocytes extracted from the pre-fed AKR mice were injected into immunodeficient (nude) mice. Human colon carcinoma cell lines were then inoculated into the nude mice. The researchers found that tumors developed more slowly in the nude mice inoculated with lymphocytes than in the nude mice without lymphocyte inoculation. The researchers concluded that the antitumorigenic activity of lentinan was indeed maintained through oral administration (J. Altern. Complement. Med. 2002;8:581–9).


Interestingly, a recent case study suggests that adoptive immunotherapy with lentinan alone might have been an effective treatment in a woman who had lymph node metastases from ovarian cancer, insofar as the regimen was maintained for 5 months without chemotherapy (Anticancer Res. 2006;26:4015–8).


C. sinensis


C. sinensis, an Ascomycetes fungus, has traditionally been consumed in China to enhance sexual performance. Researchers have demonstrated in vivo that C. sinensis and its fractions stimulate mouse testosterone production. The same researchers also showed the mushroom and its fractions stimulate steroidogenesis in primary mouse Leydig cells and MA-10 mouse Leydig tumor cells (Life Sci. 2004;75:1051–62).


Like several other mushrooms, C. sinensis exhibits immunomodulating activity. In a recent study, researchers examined the protective effect of this species against group A streptococcus (GAS) in mice. Mice that were force-fed C. sinensis mycelium extract for 3 consecutive days before GAS infection had a higher survival rate and diminished local skin-tissue injury than did mice fed phosphate-buffered saline (PBS). In addition, pretreatment with C. sinensis extract for 3 days followed by treatment with C. sinensis every other day after GAS infection yielded 100% survival. Furthermore, bacterial dissemination was observed in the blood and organs in PBS-treated mice, but not in mice treated with C. sinensis. The investigators concluded that C. sinensis mycelium extract improved survival in mice by reducing bacterial growth and dissemination (J. Med. Microbiol. 2005;54:795–802).


In a recent study, an orally administered hot-water extract of C. sinensis protected mice from bone marrow and intestinal injury after total body irradiation, increasing time to death by several days. The researchers attributed the radioprotective effect of this mushroom, in part, to its activity against free radicals; the extract lowered reactive oxygen species levels in vitro (Radiat. Res. 2006;166:900–7).


In a study with potentially more direct dermatologic implications, a compound containing a preparation of C. sinensis prolonged the survival of allogeneic grafted pigskin, possibly by inhibiting the expression of CD4(+) and CD8(+) glycoproteins and lessening the inflammatory reaction (Zhong Xi Yi Jie He Xue Bao 2006;4:185–8).


G. frondosa


Popular in Asia as a culinary and medicinal mushroom, Grifola frondosa (maitake) has been studied for its immunomodulatory activity. In one study, researchers found that the relatively low molecular mass polysaccharides isolated in hot water extracts stimulated phagocytes and augmented the cytotoxicity of natural killer cells in human peripheral blood. The authors concluded that these results buttressed the evidence for G. frondosa's immunomodulatory activity (J. Agric. Food Chem. 2006;54:2906–14).


G. frondosa is gaining recognition as a potent source of polysaccharides with health benefits. The MD fraction (MDF), a proprietary maitake polysaccharide extract thought to be a significant improvement over the preceding D fraction, along with the D fraction and other extracts, exhibited potential as an immunomodulating agent and as an adjunct to cancer and HIV treatment (Altern. Med. Rev. 2001;6:48–60).


In one study, researchers looked at the effects of MDF on nitric oxide production in a murine monocyte/macrophage cell line. They found that MDF is a novel inducer of nitric oxide synthase (iNOS), a mediator of nitric acid production. They concluded that this action partly explains MDF's antitumor activity against human hepatoma-derived huH-1 cells (J. Exp. Clin. Cancer. Res. 2001;20:591–7).


In a mouse study, investigators found the mushroom's D fraction lowered the effective dosage of the chemotherapeutic agent mitomycin C needed to control cancer by augmenting the proliferation, differentiation, and activation of immunocompetent cells (Nutrition 2005;21:624–9). In an earlier study, most of the same investigators showed the D fraction repressed metastatic cancer progression, mainly by stimulating natural killer cell activity. The team also showed that combining D fraction immunotherapy with chemotherapy cut tumor size in lung, liver, and breast cancer (J. Med. Food 2003;6:371–7).


Recently, researchers evaluated the photoprotective potential of exopolysaccharide (EPS) derived from G. frondosa. When they exposed human dermal fibroblasts to UVA, they found that EPS dose-dependently decreased matrix metalloproteinase-1 (MMP-1) expression without causing a significant cytotoxic response. The investigators concluded that by hindering MMP-1 reduction, the G. frondosa mycelial extract inhibited cutaneous photoaging in dermal fibroblasts (FEMS Microbiol. Lett. 2005;251:347–54).


At the Store


The chief dermatologic product that includes L. edodes is Aveeno's Positively Ageless Active Naturals Natural Shiitake Complex Rejuvenating Serum. It is designed to promote cell renewal and improve cutaneous signs of photoaging.


Dr. Andrew Weil has designed two products for Origins that include both C. sinensis and Ganoderma lucidum extracts. Origins Plantidote Mega-Mushroom Face Serum, and Plantidote Eye Serum, combine the mushroom species Hypsizygus ulmarius with C. sinensis and Ganoderma lucidum, along with other healthful ingredients (including ginger, turmeric, basil, resveratrol, and argan nut oil) to combat cutaneous aging.


In addition, N.V. Perricone Maitake Mushroom Extract SX Fraction contains a Grifola frondosa extract in a tablet for the treatment of metabolic syndrome. It was designed by Dr. Nicholas Perricone, a board-certified dermatologist.


Conclusions


The history and mounting evidence of the medical benefits of mushrooms are impressive. Collectively, the literature suggests that L. edodes, C. sinensis, and G. frondosa exhibit antiproliferative and immunomodulatory activity, and have potential dermatologic applications.


With continuing research, we are more likely to see studies on the cutaneous effects of various mushroom extracts. That said, much more work needs to be done to establish the direct dermatologic benefits of medicinal mushrooms. What has emerged thus far provides reasons for optimism.



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