Polyphenols of Ferula lehmanni Boiss. attenuate high-fat diet-induced liver injury by regulating lipid synthesis and remodeling the gut microbiota

Abstract

High-fat diet (HFD)-induced liver injury, characterized by hepatic steatosis, inflammation, and oxidative stress, represents a significant global health challenge. Ferula lehmannii Boiss. (FLB), an edible and medicinal plant, is rich in polyphenols and has hepatoprotective effects, but the gut microbiota-mediated mechanism remains unclear. This study elucidates the protective effects of FLB polyphenols (FLBP) against HFD-induced liver injury via the gut microbiota. Chemical profiling and network pharmacology predicted FLBP's multitarget effects on lipid metabolism and inflammation. In vivo, FLBP attenuated hepatic steatosis by regulating lipogenic factors and energy metabolism, reducing oxidative stress and enhancing antioxidants. Gut microbiota analysis showed that FLBP restored gut microbial diversity, enriched beneficial bacteria abundance and promoted short-chain fatty acid (SCFA) production. Antibiotic-induced microbiota ablation abolished the hepatoprotective effects of FLBP, confirming the essential role of the gut microbiota. Collectively, our findings demonstrate that FLBP alleviates HFD-induced liver injury by regulating hepatic lipid synthesis and remodeling the gut microbiome, highlighting its potential as a dietary intervention for managing diet-related liver diseases.