Atractylodes lancea (Thunb.) DC polysaccharide alleviates MASH by regulating the 1‑carbon cycle through intestinal flora remodelling.

Metabolic-associated steatohepatitis (MASH) is a severe stage of Metabolic-associated fatty liver disease (MAFLD). Currently, effective pharmacological therapies for MASH are extremely limited. An Atractylodes lancea (Thunb.) DC polysaccharide (ALP) was isolated from Atractylodes lancea (Thunb.) DC, and its preventive effect on MASH and the potential mechanism were investigated. Mice were fed a high-fat and methionine/choline-deficient diet (HFMCD) to induce MASH. MASH model mice were then treated with ALP at low (50 mg/kg/d) or high (100 mg/kg/d) dosages. Faecal metagenomics, nontargeted metabolomics sequencing, biochemical and pathological analyses, ELISAs, western blotting and other detection techniques were conducted to elucidate the mechanism by which ALP alleviates MASH. The research results indicate that both the low-dose (50 mg/kg/d) and high-dose (100 mg/kg/d) of ALP can effectively alleviate MASH, but the high-dose has a more significant effect. ALP effectively reduced liver lipid accumulation and inflammation in MASH model mice by regulating the 1‑carbon cycle through intestinal flora remodelling. ALP may be a promising natural candidate for the treatment of MASH.