Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy.

Pueraria Mirifica (Willd. Ohwi) is a medicine with anti-inflammatory and lipid-lowering properties. Puerarin is one of the main active components of Pueraria. The aim of this study was to investigate the possible mechanisms of Pueraria in the treatment of non-alcoholic fatty liver disease. The therapeutic effect of the drug was demonstrated by serum and liver pathology indicators. The mechanism of action of puerarin was demonstrated by intestinal microbial changes and short-chain fatty acid content tests. The mechanism of puerarin alleviating Metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal flora was predicted by bioinformatics. The relationship between flora and liver was revealed by q-PCR detection of mRNA expression level of liver metabolic genes. And the mechanism of puerarin action was further verified by intestinal microbial clearance experiments. Puerarin reduced vacuolar-like changes, lipid deposition, and inflammatory cell infiltration in the livers of high-fat diet (HFD) model mice. The gut microbiota abundance and diversity were remodeled, short-chain fatty acid content was increased, and the intestinal mucosal barrier was repaired, accompanied by a reduction in inflammatory cytokines. Puerarin regulated mRNA expression of hepatic lipid metabolism genes to alleviate MASLD. These results suggested that puerarin treats MASLD by treating altering bacterial metabolism and anti-inflammation.