Sea Buckthorn Pericarp Flavonoids Improve Diet-Induced Hyperlipidemia via Coordinated Modulation of Hepatic Lipid Metabolism and Gut Microbiota

Sea buckthorn pericarp pomace, a major by-product of juice processing, represents a promising food-grade source of bioactive flavonoids. This study investigated the hypolipidemic effects and underlying mechanisms of total flavonoids extracted from Sea buckthorn pericarp pomace (TFSP) in mice with high-fat diet (HFD)-induced hyperlipidemia. TFSP intervention significantly suppressed body weight gain and improved serum lipid profiles by reducing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Hepatic lipid accumulation and injury were alleviated, accompanied by enhanced activities of antioxidant enzymes (SOD, CAT, GSH-Px) and reduced oxidative stress markers. At the molecular level, TFSP downregulated key lipogenic proteins—including ACC and FAS—and upregulated markers of fatty acid oxidation and triglyceride hydrolysis—namely CPT-1α, PPARα, and ATGL. Moreover, TFSP restored HFD-induced gut microbiota dysbiosis, increased the relative abundance of beneficial genera such as Akkermansia, and decreased that of potentially harmful taxa including Allobaculum. These findings demonstrate that TFSP—a value-added food processing by-product—ameliorates hyperlipidemia through coordinated regulation of hepatic lipid metabolism and gut microbial composition, supporting its potential application as a natural, food-derived ingredient in lipid-lowering functional foods.