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The Medicinal Mushroom Ganoderma neo-japonicum (Agaricomycetes) from Malaysia: Nutritional Composition and Potentiation of Insulin-Like Activity in 3T3-L1 Cells

Subramaniam S, Sabaratnam V, Heng CK, Kuppusamy UR

Int J Med Mushrooms, 2020;22(1):65-78.
PMID: 32463999 DOI: 10.1615/IntJMedMushrooms.2020033250

Ganoderma neo-japonicum is an annual polypore mushroom that is consumed by Malaysian indigenous tribes to treat various ailments including diabetes. The present study aimed to investigate the nutritive composition and in vitro antihyperglycemic effects of G. neo-japonicum extracts on 3T3-L1 preadipocytes. Nutritional analysis of G. neo-japonicum basidiocarps indicated a predominant presence of carbohydrates, proteins, dietary fiber, and microelements. Hot aqueous extract (AE) and its isolated (1,3)(1,6)-β-D-glucan polysaccharide (GNJP) from basidiocarps of G. neo-japonicum were evaluated for their ability to stimulate insulin independent adipogenesis, glucose uptake, adiponectin secretion, and regulate gene expression in 3T3-L1 adipocytes. GNJP showed a dose dependent stimulation of glucose uptake and adiponectin secretion but attenuated lipid accumulation in 3T3-L1 adipocytes. It upregulated the expressions of adiponectin, Aktl (protein kinase B), PPARγ (peroxisome proliferator activated receptor gamma), PRKAG2 (protein kinase, AMP activated), and Slc2a4 (glucose transporter) genes to stimulate glucose uptake in 3T3-L1 cells, which may have contributed to the insulin-mimicking activities observed in this study. In summary, the nutritive compositions and significant glucose uptake stimulatory activities of GNJP indicated that it may have potential use in the formulation of functional food for the management of hyperglycemia, insulin resistance, and related complications.

Matched MeSH terms: Glucans/pharmacology
Restitution of epithelial cells during intestinal mucosal wound healing: The effect of a polysaccharide from the sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden

Veeraperumal S, Qiu HM, Tan CS, Ng ST, Zhang W, Tang S, et al.

J Ethnopharmacol, 2021 Jun 28;274:114024.
PMID: 33727110 DOI: 10.1016/j.jep.2021.114024

ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerotis (Cooke) Ryvarden cultivar TM02, also known as tiger's milk mushroom, is regarded as important folk medicine in Malaysia, while is used for the treatment of liver cancer, chronic hepatitis, gastric ulcer in traditional Chinese medicine. However, there is no compilation of scientific evidence that its protection for gastric, and no attempts have been made to understand how polysaccharides in Lignosus rhinocerotis might promote intestinal mucosal wound healing.
AIM OF THE STUDY: This study aimed to investigate the effect and mechanism of β-glucan prepared from L. rhinocerotis using an enzymatic method on epithelial restitution during intestinal mucosal damage.
MATERIALS AND METHODS: Based on FT-IR, MALDI-TOF-MS, HPSEC-MALLS-RID, and AFM, the structure of polysaccharides from L. rhinocerotis was analysed. In addition, polysaccharides were used to test for wound healing activity in IEC-6 cells by measuring cell migration, proliferation, and expression of cell division control protein 42, Rac-1, RhoA, and Par-3.
RESULTS: β-glucan was extracted using enzyme-assisted extraction, and a yield of approximately 8.5 ± 0.8% was obtained from the dried biomass. The β-glucan extracted by enzyme-assisted extraction (EAE) of polysaccharides was composed entirely of D-glucose with a total carbohydrate content of 95.5 ± 3.2%. The results of HPLC, FTIR, and MALDI-TOF-MS analyses revealed EAEP to be confirmed as β-glucan. The molecular weight of prepared β-glucan was found to be 5.315 × 104 g/mol by HPSEC-MALLS-RID. Furthermore, mucosal wound healing studies showed that the treatment of IEC-6 with a β-glucan concentration of 200 μg/mL promoted cell migration and proliferation, and it enhanced the protein expression of cell division control protein 42, Rac-1, RhoA, and Par-3.
CONCLUSIONS: The present study reveals that the prepared β-glucan accelerates intestinal epithelial cell proliferation and migration via activation of Rho-dependent pathway. Hence, β-glucan can be employed as a prospective therapeutic agent for the treatment of diseases associated with gastrointestinal mucosal damage, such as peptic ulcers and inflammatory bowel disease.

Matched MeSH terms: beta-Glucans/pharmacology*
TRAIL-based tumor sensitizing galactoxyloglucan, a novel entity for targeting apoptotic machinery

Aravind SR, Joseph MM, George SK, Dileep KV, Varghese S, Rose-James A, et al.

Int J Biochem Cell Biol, 2015 Feb;59:153-66.
PMID: 25541375 DOI: 10.1016/j.biocel.2014.11.019

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for cancer therapy due to its ability to selectively induce apoptosis in cancer cells, without causing significant toxicity in normal tissues. We previously reported that galactoxyloglucan (PST001) possesses significant antitumor and immunomodulatory properties. However, the exact mechanism in mediating this anticancer effect is unknown. This study, for the first time, indicated that PST001 sensitizes non-small cell lung cancer (A549) and nasopharyngeal (KB) cells to TRAIL-mediated apoptosis. In vitro studies suggested that PST001 induced apoptosis primarily via death receptors and predominantly activated caspases belonging to the extrinsic apoptotic cascade. Microarray profiling of PST001 treated A549 and KB cells showed the suppression of survivin (BIRC5) and anti-apoptotic Bcl-2, as well as increased cytochrome C. TaqMan low density array analysis of A549 cells also confirmed that the induction of apoptosis by the polysaccharide occurred through the TRAIL-DR4/DR5 pathways. This was finally confirmed by in silico analysis, which revealed that PST001 binds to TRAIL-DR4/DR5 complexes more strongly than TNF and Fas ligand-receptor complexes. In summary, our results suggest the potential of PST001 to be developed as an anticancer agent that not only preserves innate biological activity of TRAIL, but also sensitizes cancer cells to TRAIL-mediated apoptosis.

Matched MeSH terms: Glucans/pharmacology*
Pink oyster mushroom Pleurotus flabellatus mycelium produced by an airlift bioreactor-the evidence of potent in vitro biological activities

Klaus A, Wan-Mohtar WAAQI, Nikolić B, Cvetković S, Vunduk J

World J Microbiol Biotechnol, 2021 Jan 04;37(1):17.
PMID: 33394203 DOI: 10.1007/s11274-020-02980-6

Four types of mycelial extracts were derived from the airlift liquid fermentation (ALF) of Pleurotus flabellatus, namely exopolysaccharide (EX), endopolysaccharide (EN), hot water (WE), and hot alkali (AE) extracts. Such extracts were screened for their active components and biological potential. EN proved to be most effective in inhibition of lipid peroxidation (EC50 = 1.71 ± 0.02 mg/mL) and in Cupric ion reducing antioxidant capacity (CUPRAC) assay (EC50 = 2.91 ± 0.01 mg TE/g). AE exhibited most pronounced ability to chelate ferrous ions (EC50 = 4.96 ± 0.08 mg/mL) and to scavenge ABTS radicals (EC50 = 3.36 ± 0.03 mg TE/g). β-glucans and total phenols contributed most to the chelating ability and quenching of ABTS radicals. Inhibition of lipid peroxidation correlated best with total glucans, total proteins, and β-glucans. Total proteins contributed most to CUPRAC antioxidant capacity. Antifungal effect was determined against Candida albicans ATCC 10231 (MIC: 0.019-0.625 mg/mL; MFC: 0.039-2.5 mg/mL), and towards C. albicans clinical isolate (MIC and MFC: 10.0-20.0 mg/mL). Comparison of cytotoxicity against colorectal carcinoma HCT 116 cells (IC50: 1.8 ± 0.3-24.6 ± 4.2 mg/mL) and normal lung MRC-5 fibroblasts (IC50: 17.0 ± 4.2-42.1 ± 6.1 mg/mL) showed that EN, and especially AE possess selective anticancer activity (SI values 3.41 and 9.44, respectively). Slight genotoxicity was observed only for AE and EX, indicating the low risk concerning this feature. Notable antioxidative and anticandidal activities, selective cytotoxicity against colorectal carcinoma cells, and absence/low genotoxicity pointed out that ALF-cultivated P. flabellatus mycelium could be considered as a valuable source of bioactive substances.

Matched MeSH terms: beta-Glucans/pharmacology