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Fungal Polysaccharides and Metabolites as immunomodulators Basidiomycetes and polysaccharides In traditional oriental and folk medicine, various kinds of fungi belonging to basidiomycetes have been used as remedies for cancer. Following this lead, Chihara of the National Cancer Center Research Institute of Japan and his coworkers in 1969 first reported marked antitumor activity of a polysaccharide from Lentinus edodes (Berk) Sing., the most popular edible mushroom in Japan and China. And named it lentinan.
In the same year Ikekawa er al. reported the antitumor activities of aqueous extracts of seven different edible mushrooms against sarcoma-180 ascites tumor in mice. The percentage inhibition of this tumor ranged from 43 to 92% following intraperitoneal injection of 200 mg/kg/day of th3 water extracts fir ten days. Lentinan has been most extensively investigated, excellent reviews are available on the chemical, biological, immunological and clinical studies of this compound {7,8}.
Lentinan has been proven to be a beutral polysaccharide. It is fully purified B-1,3-d-glucan with B-1,6-branching{8}. X-ray analysis of the solid sample revealed a right-handed triple helical structure, with a hexagonal lattice constyants of ……. The table 3 summarizes the immunomoduating polysaccharides from nine different fungi{11-38}. It is worth noting that most of the active components have B-(1-6) glucose or a-(1-4) glucose as the side chain. The notable exception in the galactomannan derived from Cordyceps cicadae. It has a-D-(1---2), a-(1-6) configurations in the main chain and B-D-(1-2) configuration in the side chain{38}.
Lentinan and Its Mode of Action Among the fungal polysaccharides, lentinan is the most extensively studied compound. It has been shown to exert significant antirumor effect and to prevent chemical and viral oncogenesis. Lentinan has been proven to have significant antitumor and metastasis-inhabiting effects in allogeneic and autochthonous hosts, and its unique mode of action has been exhaustively investigated. Many acute, semi-acute and chronic toxicological studies have been completed in animal models.
The antitumor effect is host-mediated. It represents a unique class of immunopotentiators. It is a T cell-oriented adjuvant. In vivo lentinan triggers the increased production of various bioactive serum factors associated with immunity and inflammation, such as interlukene-1 (IK-1), interlukene-3 (IL-3), colony stimulating factor (CSF), vascular dilation inducer, and acute-phase protein inducer, etc. These effects are produced either by the direct impact of macrophages or indirectly via lentinan-stimulated T cells, which initiate the induction of many immunological changes in the host. Enhanced IL-1 production promotes the maturation of immature effector cells to mature cells capable of responding to lymphkines like IL-2 and T cell-replacing factors. This mechanism of action requires intact t cell system for antitumors activity of lentinan.
Conclusion For thousand of years Fu Zheng (supporting the normal and) and Chei Shei (gertting rid of the abnormal) herbs have been used in cancer therapy and treatment of verious diseases in Chinese traditional medicine. Only recently have the biochemical and pharmacological basses of the immunological effects of some Chinese herbs and polysaccharides from edible mushrooms been elucidated. Many of the Fu Zheng herbs and fungal metabolites, especially polysaccharides, have been shown to stimulate cellular immunity functions. Promising clinical result have been shown by Taguchi et al. In a randomized control study of lentinen (from Lentinus edodes) in phases III on patients with advanced and recurrent stomach and colorectal cancer.
Other preparations and chemical substances from various species of fungi like Poria cocos, Polyporuss umbellatus, Ganoderma lucidum, G. applanatum, G. Japonium, Cordyceps ophioglossoides, C. sinensis, C. cicadae, polyporus eresicolor…. Have also been shown to have definitive immunomodulation effects and antitumor activities. It is expected that with recently developed new technologies in immunology and molecular biology, and the urgent needs in developing preventive and therapeutic agents for diseases associated with immune deficiencies, especially AIDS, these natural products may provide new leads in the development of new drugs.
From accumulated data it appears that the following characteristics are all important for immunostimulationg properties of fungal polysaccharides: 1. The Primary structure of the polysaccharides,
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