Bofutsushosan (Fangfengtongshengsan) improves early stages of NASH via the gut–liver axis in diabetes-induced NASH model mice

Abstract

BackgroundThe mechanisms underlying non-alcoholic fatty liver disease (NAFLD) are not fully understood, but the gut microbiota is deeply involved. Because the Japanese traditional medicine bofutsushosan (BTS; Fangfengtongshengsan in Chinese) is known to improve obesity-induced liver injury and increase gut Akkermansia muciniphila, we evaluated its effects in a mouse model of diabetes-induced nonalcoholic steatohepatitis (NASH). MethodsTwo-day-old male C57BL/6J mice were injected subcutaneously with streptozotocin and fed a high-fat diet (HFD) from 4 weeks. Between 5 and 8 weeks, HFD was supplemented with 5% BTS (BTS) or not supplemented (CONT), and plasma, liver, and stool samples were collected and analyzed. ResultsThe NAFLD activity score (NAS), which was consistent with early steatohepatitis in CONT mice, was significantly lower in BTS mice (P=0.018). Improvement of steatosis contributed most to decreasing NAS. Relative abundances of probiotic Akkermansia muciniphila and Bifidobacterium pseudolongum were significantly higher in BTS mice (both P<0.05). Positive correlations were observed among NAS, steatosis, ballooning, and body weight change. Liver macrophage markers correlated with some microbes in BTS mice. ConclusionsBTS administration suppressed liver steatosis and improved the gut microbiome, which correlated with some liver factors. BTS may be a promising treatment for NAFLD by maintaining the gut–liver axis.