ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, G. lucidum polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of G. lucidum polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.
AIMS OF THE STUDY: This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from G. lucidum in the treatment of NAFLD and to elucidate its underlying mechanisms.
MATERIALS AND METHODS: The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.
RESULTS: The backbone of EPGLa consists of the following glycosidic linkages: →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →3,6)-β-D-Manp-(1→, →2)-α-D-Manp-(1→, and →4)-β-D-Galp-(1 → . Its branches are composed of β-D-Glcp-(1→, β-D-Glcp-(1 → 3)-β-D-Glcp-(1→, and α-L-Fucp-(1 → . In vivo results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.
CONCLUSION: Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.
