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For four thousand years, enzyme-rich Reishi mushroom ( Ganoderma Lucidum) have been used as part of Japanese and Chinese medicine, especially in the treatment of chronic hepatitis, nephritis, hepatopathy, neurasthenia, arthritis, bronchitis, asthma, gastric ulcer, and insomnia.  According to Christopher Hobbs (Medicinal Mushrooms, Santa Cruz, CA: Botanica Press, 1995), whole Reishi extracts have demonstrated a number of pharmacological effects (either in vivo or in vitro), including analgesic, anti-allergy, bronchitis preventative, anti-inflammatory, antibacterial, antioxidant, antitumor, antiviral, blood-pressure lowering, bone marrow enhancing, cardiotonic, central nervous system depressant and peripheral anticholinergic, expectorant and antitussive immune-stimulating, anti-HIV and adrenocortical effects.

 

Ganoderma lucidum (Leys. ex Fr.) Karst;  Ling-zhi; Reishi.

This mushroom was the most rare and valuable herb in Chinese medicine, it is known in China for over 4,000 years as Ling zhi. It was considered among the most powerful natural healing herbs in Orient, it was very rare and expensive to obtain until recent development of high density cultivation technique. Ganoderma lucidum, (ling zhi, Reishi) is rich in organic compounds such as polysaccharide, amino acid, triterpines, ascorbic acid, sterols, lipids, alkaloids, and trace minerals. These compounds are being studied for their effect on the immune system.

Dennert and Tucker, 1973; Hirai et al., 1993 Xiao et al., 1993 reported that Ganoderma lucidum (Gl), a Chinese herb, could promote longevity and maintain vitality. G.l. also influenced the immune status of hemophiliacs with positive HIV antibody, and reversed helper suppressor T-lymphocyte ratio.

Effects of Ganoderma Lucidum and Krestin (PSK) on Cellular Immunocompetence in r-ray-irradiated Mice. The effects of Ganoderma lucidum (GI) and Krestin(PSK) extracts on cellular immunocompetence, leukocyte counts and differential count in r-irradiated mice were investigated in the study. ICR train male mice were used and randomly divided into five groups. Group A is normal control. Group B, the experimental control, was treated with GL. Group C, the radiation treatment control, was treat with whole body exposure to 4 Gy r-irradiation (RT). Group D. was treated wit RT and Gl. Group E was treated with RT and PSK. The dosage of Gl was 400 mg/day/kg body weight and PSK was 500 mg/day/kg body weight. Cellular immunocompetence was measured by means of 3H-thymidine incorporation with splenic cells stimulated through mitogens such as PHA. Con A and LPS. The results revealed that relative splenic weight in Group D and E. were higher than group C on day 28 after r-irradiation, Group D was the highest in all the experimental groups. Leukocyte counts were decreased significantly in Groups D and E. on day 7.  Gl administration showed an increase in the leukocyte count in Group D on day 28. The blastogenic response of splenocytes to PHA and Con A in groups D and E were higher than in Group C on day 7 and 28. We suggested that Gl and PSK were effective in enhancing the recovery of cellular immunocompetence from r-irradiation. Wang-chi Chen, Dou-mong Hau, and Shiuh-Sheng Lee, Institute of Radiation Biology, National Tsing Hua University, Hsin Chu, Taiwan, American Journal of Chinese Medicine, Vol. XXIII, No. 1, pp 71-80.

 

Antifibrotic effects of a polysaccharide extracted from Ganoderma lucidum, glycyrrhizin, and pentoxifylline in rats with cirrhosis induced by biliary obstruction., For the past few years, we have been investigating polysaccharides from Ganoderma lucidum as antifibrotic agents. In a previous study, we discovered that polysaccharides extracted from G. lucidum lowered the collagen content in liver but had no effect on serum biochemical parameters in rats subjected to bile duct ligation and scission-induced fibrosis. In this study, we changed the extraction method and obtained polysaccharides extracted from G. lucidum. The polysaccharide from G. lucidum reduced the serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin and also reduced the collagen content in liver and improved the morphology. Pentoxifylline, which is reported to exhibit an antifibrotic effect in pigs with fibrosis induced by yellow phosphorus, did not have any antifibrotic effects in fibrosis induced by biliary obstruction. Glycyrrhizin, which is used in the treatment of hepatitis, reduced serum ALT and AST values but there was no significance. It had no effect on liver hydroxyproline content which implies that glycyrrhizin has no antifibrotic effect in the rats with fibrosis induced by bile duct ligation and scission. These data suggest that the polysaccharide from Ganoderma lucidum could be a promising antifibrotic agent. However, further study is needed to understand the inhibition mechanism of collagen deposition of polysaccharides from Ganoderma Iucidum and its clinical applicability remains to be established. ,Park EJ; Ko G; Kim J; Sohn DH , College of Pharmacy, Medicinal Resources Research Center, Wonkwang University, Iksan, Geonbuk, Korea. , Biol Pharm Bull, 20(4):417-20 1997 Apr .

 

Differentiation and grouping of isolates of the Ganoderma lucidum complex by random amplified polymorphic DNA-PCR compared with grouping on the basis of internal transcribed spacer sequences., Laccate polypores of the Ganoderma lucidum species complex are widespread white rot fungi of economic importance, but isolates cannot be identified by traditional taxonomic methods. Parsimony analysis of nucleotide sequences from the internal transcribed spacers (ITS) of the ribosomal gene (rDNA) distinguished six lineages in this species complex. Each ITS lineage may represent one or more putative species. While some isolates have identical ITS sequences, all of them could be clearly differentiated by genetic fingerprinting using random amplified polymorphic DNA (RAPD). To investigate the suitability of RAPD markers for taxonomic identification and grouping of isolates of the G. lucidum complex, RAPD fragments (RAPDs) were used as phenotypic characters in numerical and parsimony analyses. Results show that data from RAPDS do not distinguish the same clades as ITS data do. Groupings based on analysis of RAPD data were very sensitive to the choice of the grouping method used, and no consistent grouping of isolates could be proposed. However, analysis with RAPDs did resolve several robust terminal clades containing putatively conspecific isolates, suggesting that RAPDs might be helpful for systematics at the lower taxonomic levels that are unresolved by ITS sequence data. The limitations of RAPDs for systematics are briefly discussed. The conclusion of this study is that ITS sequences can be used to identify isolates of the G. lucidum complex, whereas RAPDs can be used to differentiate between isolates having identical ITS sequences. The practical implications of these results are briefly illustrated., Hseu RS; Wang HH; Wang HF; Moncalvo JM , Department of Agricultural Chemistry, National Taiwan University, Taipei, Republic of China., Appl Environ Microbiol, 62(4):1354-63 1996 Apr

 

The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes., The present study was to ascertain the immunomodulating and anti-tumor effects of Ganoderma (G.) lucidum. Polysaccharides (PS) from fresh fruiting bodies of G. lucidum (PS-G) were isolated and used to potentiate cytokine production by human monocytes-macrophages and T lymphocytes. Our results had shown that the levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)- alpha, and IL-6 in macrophage cultures treated with PS-G (100 micrograms/ml) were 5.1-, 9.8- and 29-fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)- gamma from T lymphocytes was also greatly promoted in the presence of PS-G (25-100 micrograms/ml). Furthermore, these cytokine-containing mononuclear cell-conditioned media (PSG-MNC-CM) were found to suppress the proliferation and clonogenicity of both the HL-60 and the U937 leukemic cell lines. DNA labeling and gel electrophoresis showed that treatment with PSG-MNC-CM markedly induced leukemic-cell apoptosis. Flow-cytometric analysis revealed that few (2.3 +/- 0.8%) apoptotic cells were seen in the control cultures, while PSG-MNC-CM treatment resulted in a significant increase in the apoptotic population both in the HL-60 (38.3 +/- 4.5%) and in the U937 (44.5 +/- 3.8%) cells. In addition, 40 to 45% of the treated leukemic cells were triggered to differentiate into mature monocytic cells expressing CD14 and CD68 surface antigens. However, PS-G alone had no such effects even at a higher dose of 400 micrograms/ml. Since untreated macrophages and T lymphocytes produced little or no cytokine, and normal MNC-CM did not suppress leukemic cell growth, it was suggestive that the anti-tumor activity of PSG-MNC-CM was derived from the elevated levels of cytokines. Antibody-neutralization studies further revealed that the anti-tumor cytokines in the PSG-MNC-CM were mainly of TNF- alpha and IFN- gamma, and these 2 cytokines acted synergistically on the inhibition of leukemic-cell growth., Wang SY; Hsu ML; Hsu HC; Tzeng CH; Lee SS; Shiao MS; Ho CK ,Department of Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China., Int J Cancer, 70(6):699-705 1997 Mar 17

 

Production of carpophores of Lentinus edodes and Ganoderma lucidum grown on cork residues. , Cork, being widely used in industry, generates high amounts of waste of difficult elimination because of its complex biological degradation, and the high pollutant smokes from its burning. Similarities between suberin (major component of cork) and lignin suggest that fungi with high lignin degrading capacity could colonize cork residues. Basidiomycetes such as Lentinus edodes and Ganoderma lucidum, besides their capacity for degrading, are edible. Thus, while using them to degrade cork, it is also possible to obtain a food product. In this study, dry matter was reduced 40%, suberin was degraded 45%, oxidizable carbon was increased 35%, and Lentinus showed a high rate of growth. These results indicate that there is an environmental alternative to the elimination of residues from the cork industry, Riu H; Roig G; Sancho J , Departament d'IndŽustries Agroaliment`aries, Escola Superior d'Agricultura de Barcelona, Universitat Polit`ecnica de Catalunya, Espa~na. , Microbiologia, 13(2):185-92 1997 Jun

 

Suppressive effects of Ganoderma lucidum on proliferation of peripheral blood mononuclear cells. , The basidiocarps of Ganoderma lucidum have been used for prevention and treatment of various diseases in the Orient. Methanolic extracts of this mushroom were applied to human peripheral blood mononuclear cell (PBMC) culture systems in the presence of various immunostimulating or immunosuppressive agents. Phytohemagglutinin-induced cell proliferation was reduced to 14% of that of the control by a GLE fraction that is the neutral component of the methanolic extracts of the carpophores. 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell proliferation was inhibited by the fractions of GLA, GLC, GLE and GLG. However none of these fractions inhibited proliferation of the PBMCs stimulated with TPA plus ionomycin (IM). Treatment of the PBMCs with cyclosporin A (CsA) led to blockage of the cell proliferation to 9% of that of the control. When the cells were cultured with the methanolic fractions in the presence of CsA, concentration dependent inhibition of the cell proliferation was observed by the addition of GLE and GLG fractions. On the contrary, the GLH fraction recovered the CsA induced inhibition of the cell proliferation. Taken together, among the methanolic fractions, GLE showed the highest inhibitory activity. This fraction might inhibit the protein kinase C signal pathway and accelerate the CsA signal pathway. ,Kim RS; Kim HW; Kim BK , Department of Microbial Chemistry, College of Pharmacy, Seoul National University, Korea. , Mol Cells, 7(1):52-7 1997 Feb 28 .

 

Effects of Ganoderma lucidum and krestin on subset T-cell in spleen of gamma-irradiated mice., Effects of Ganoderma lucidum (Gl) and Krestin (PSK) extracts on spleen, thymus and splenocytes in gamma-irradiated mice were investigated in this study. ICR strain male mice were divided into five groups. Group A was the normal control. Group B, the experimental control, was treated with Gl. Group C, the radiation treatment control, was treated with whole body exposure to 4 Gy gamma-irradiation (RT). Group D was treated with RT and Gl. Group E was treated with RT and PSK. The dosage of Gl was 400 mg/day/kg body weight and PSK was 500 mg/day/kg body weight. Our results indicated that the relative thymus weight in groups D and E were higher than group C on day 28 after gamma-irradiation. Group D was the highest in all the experimental groups. CD4 and CD8 splenocytes in group D were higher than group C on days 7 and 28. Gl was better than PSK in repairing the damage of subset T-cells in the spleen of gamma-irradiated mice. ,Chen WC; Hau DM; Wang CC; Lin IH; Lee SS , Institute of Radiation Biology, National Tsing Hua University, Hsinchu, Taiwan. , Am J Chin Med, 23(3-4):289-98 1995

 

Natural inhibitors for protein prenyltransferase., Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras oncoprotein. Prenylation of this residue is essential for membrane association and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated to inhibit Ras-dependent cell transformation and thus represent a potential therapeutic strategy for the treatment of human cancers (1). In the present study, the inhibitory principles for protein prenyltransferases were isolated and identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma lucidum were identified as ganoderic acid A and ganoderic acid C by comparison with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM against FPT and its methyl ester (methyl ganoderate A) has an IC50 value of 38 microM for the same enzyme. These inhibitors appear to be competitive with farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and methyl ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from garlic were identified as diallyl thiosulfinate (allicin), methyl allyl thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50 values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP) and its Ki was determined to be 15 microM. The molecular structures of triterpenes and thiosulfinates are expected to be useful in designing lead compounds for new potent antitumour agents. ,Lee S; Park S; Oh JW; Yang C , Department of Chemistry, College of Natural Sciences, Seoul National University, Republic of Korea. , Planta Med, 64(4):303-8 1998 May

 

Trial of a new medium-term model using benzo(a)pyrene induced lung tumor in newborn mice., A new medium-term in vivo model was tried using pulmonary adenoma induced by benzo(a)pyrene (BP) in newborn mice. Both inbred mice such as C57BL/5J, C57BR/cdJ. A/J mice and non inbred N:GP(S) mice were used. Benzo(a)pyrene was injected in the subscapular region of newborn mice within 24 hours after birth at a dose of 0.5 mg and 1 mg per mouse, respectively. After 9 weeks lung tumor induced in N:GP(S) and A/J mice but in the other mice. The dose showing a 50% tumor incidence was found in N:GP(S) mice to be 0.5 mg of BP but the tumor incidence was very high in A/J mice even at 40 micrograms of BP, the lowest dose in this experiment. To verify the utility of this model, ascorbic acid, carrot, beta carotene, soybean lecithin, spinach, Sesamum indicum, Ganoderma lucidum, caffeine, red ginseng extract, fresh ginseng and 13-cis retinoic acid, some of which are known to have anticarcinogenic activity in various animal models, were tried with this system. Ascorbic acid, soybean lecithin, Ganoderma lucidum, caffeine and red ginseng extract showed inhibition of lung tumor incidence, while fresh ginseng, carrot, beta carotene, spinach and 13-cis retinoic acid did not. This result suggested that the 9-week medium-term model using lung tumor induced by 0.5 mg of BP was useful for the screening of cancer preventive agents. ,Yun TK; Kim SH; Lee YS , Laboratory of Cancer Pathology, Korea Cancer Center Hospital, Seoul. , Anticancer Res, 15(3):839-45 1995 May-Jun

 

Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. The free radical scavenging and antihepatotoxic activity from Ganoderma lucidum, Ganoderma formosanum and Ganoderma neo-japonicum were studied. Treatment with the water extract of Ganoderma lucidum, Ganoderma formosanum and Ganoderma neo-japonicum caused a marked decrease in the CCl4-induced toxicity in rat liver, made evident by their effect on the levels of glutamic oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) in the serum. The scavenging potency of the water extracts of the crude drugs was evaluated in terms of their ability to reduce the peaks of spin adducts using electron spin resonance (ESR) spin-trapping techniques. The results indicated that Ganoderma formosanum showed the greatest antihepatotoxic activity and the greatest free radical scavenging activity. ,Lin JM; Lin CC; Chen MF; Ujiie T; Takada A ,Graduate Institute of Natural Products, Kaohsiung Medical College, Taiwan, R.O.C. , J Ethnopharmacol, 47(1):33-41 1995 Jun 23