Synergistic effects of ferulic acid and wogonin on cholestatic liver injury via gut microbiota modulation

Abstract Cholestasis, a bile flow disorder common to many liver diseases, currently lacks effective treatments. Emerging evidence links gut microbiota disturbances to cholestatic liver injury. Here, an antibiotic cocktail (ABX)-treated mouse model confirmed the indispensable role of the intestinal microbiota, with marked shifts including increased Alistipes putredinis (A. putredinis) and decreased Clostridium spp. (C. spp.). In vitro, ferulic acid and wogonin effectively modulated the gut flora, and in vivo they alleviated liver injury. Administration of A. putredinis exacerbated hepatic inflammation by disrupting intestinal barrier integrity and facilitating bacterial translocation, an effect reversed by ferulic acid. Conversely, treatment with C. spp. and wogonin enhanced bile salt hydrolase activity and bile acid excretion. Notably, combined treatment with ferulic acid and wogonin or C. spp. significantly ameliorated cholestatic liver injury. These findings underscore the critical role of gut microbiota in cholestasis and suggest therapeutic potential for microbiota-targeted and natural compound-based interventions.