A glucan from Ganoderma lucidum: Structural characterization and the anti-inflammatory effect on Parkinson's disease via regulating dysfunctions of intestinal microecology and inhibiting TLR4/MyD88/NF-κB signaling pathway

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Curtis) P. Karst (G. lucidum) is a traditional Chinese medicinal fungus, used to exert a beneficial effect on central nervous system, such as Parkinson's disease (PD). Polysaccharide is its main active ingredient, but the structural characterization and the mechanisms of the beneficial effect on PD remain to be elucidated. AIM OF THE STUDY: To obtain a purified G. lucidum polysaccharide and elucidate its structure, investigate the anti-inflammatory effect on PD and explore its potential mechanisms. MATERIALS AND METHODS: The structure of polysaccharide was analyzed through methylation analysis and NMR analysis. The anti-inflammatory effect on PD were explored in a MPTP-induced mouse model. A comprehensive microbiota-gut-metabolomics analysis was executed and subsequently deliberated, focusing on the regulation of dysfunctions of intestinal microecology. The potential mechanisms were investigated using a LPS-induced Caco-2 cell model. RESULTS: A purified glucan, GLPZ-2 was obtained. GLPZ-2 was with triple helical structure and its backbone was found to be primarily composed of 1,6-α-D-Glcp, 1,4-α-D-Glcp, 1,4,6-α-D-Glcp and 1,3,6-β-D-Glcp, with branches at the C-3 and C-4 position by t-α-D-Glcp. PD mice experiments showed that GLPZ-2 could improve motor symptoms, reduce pathological damage and decrease brain protein expression of α-Syn, IL-6, IL-1β and TNF-α. GLPZ-2 also could regulate the gut microbiota and fecal metabolites to restore to normal trend, increase SCFAs content and inhibit TLR4/MyD88/NF-κB pathway in intestine. CONCLUSIONS: GLPZ-2 exhibits an anti-inflammatory effect on PD, which provide a foundational basis for the application of GLPZ-2 as an effective drug to prevent and delay PD.