Small-Leaved Kuding Tea Extract Fractions Attenuate Hyperlipidemia and Hepatic Steatosis in Mice: Association with Upregulation of Fatty Acid β-Oxidation Enzymes and Improvement of Metabolic Biomarkers

Background/Objectives: Hyperlipidemia is a prevalent metabolic disorder that increases cardiovascular disease risk and is associated with lipid accumulation, inflammation, and oxidative stress. Small-leaved Kuding tea (SLKT) has multiple health benefits, but its lipid-lowering mechanisms remain unclear. This study evaluated the therapeutic effects of different SLKT fractions on hyperlipidemia and investigated their modulation of the fatty acid degradation pathway. Methods: A hyperlipidemia mouse model was established using a high-fat diet for 8 weeks. Sixty successfully modeled mice were randomly divided into six groups: model control, anhydrous ethanol fraction (SLK-AE), ethyl acetate fraction (SLK-EA), n-butanol fraction (SLK-NA), water-soluble fraction (SLK-WA), and simvastatin (positive control). Mice received daily gavage for 8 weeks. Serum biochemical indices, inflammatory factors, hepatic oxidative stress markers, and liver histopathology were assessed. Protein expression levels of ACADM, EHHADH, and HADHB in the liver were detected by Western blot. Results: SLKT fractions significantly reduced body weight, fat mass, serum TC, TG, LDL-C, Glu, NEFA, ALT, AST, TNF-α, IL-1β, IL-6, and LPS, while increasing HDL-C (p < 0.05). Hepatic TC, TG, ALT, AST, and MDA decreased, and SOD increased (p < 0.05). Histological staining revealed markedly reduced lipid droplets in hepatocytes. Furthermore, SLKT significantly upregulated hepatic protein expression of ACADM, EHHADH, and HADHB, key enzymes in fatty acid β-oxidation (p < 0.05). Conclusions: SLKT effectively ameliorates hyperlipidemia by improving lipid profiles, reducing serum biomarkers of liver injury and pro-inflammatory cytokines, and upregulating key fatty acid degradation enzymes. These findings support SLKT as a potential natural therapeutic agent for hyperlipidemia and associated metabolic disorders.