Chemical Composition Analysis and Hypolipidemic Activity of Polyphenols Isolated from Small-Leaved Kuding Tea

Hyperlipidemia is a widespread metabolic disease that triggers abnormal lipid accumulation. Plant polyphenols possess great potential for lipid metabolism regulation. Small-leaved kuding tea (Ligustrum robustum Roxb. Blume, SLKDT) is abundant in polyphenols with proven hypolipidemic activity, whereas its key active constituents and molecular targets remain unclear. This study aimed to identify the key active components and core targets responsible for the lipid-lowering effects of SLKDT polyphenols. Response surface methodology (RSM) was employed to optimize the extraction process of SLKDT polyphenols. In vitro cell experiments were performed to verify the lipid-lowering effect of SLKDT polyphenols, while the obtained polyphenols were further qualitatively characterized via LC-MS/MS. Furthermore, network pharmacology prediction combined with molecular docking was used to screen the key bioactive compounds and their target proteins associated with lipid metabolism regulation. Under the optimal extraction conditions (43% ethanol concentration, ultrasound time of 40 min, solid-to-liquid ratio of 1:56 g/mL, and ultrasonic temperature of 57 °C), the yield of polyphenols from SLKDT was 131.88 mg/g. In vitro experiments confirmed that SLKDT polyphenols significantly reduced intracellular lipid accumulation in HepG2 cells, increased the activities of antioxidant enzymes including GSH-PX, CAT, and T-SOD, and decreased MDA content. Furthermore, SLKDT polyphenols markedly downregulated the expression of lipid synthesis-related genes, including ACC, HMGCR, SREBP-1c, and FASN, while upregulating CYP7A1 expression. A total of 88 compounds were Preliminary identified by LC-MS/MS, mainly including glycosides, flavonoids and phenolic acids. Network pharmacology analysis revealed that chrysin, 6-demethoxytangeretin, bavachinin, isobavachin, and bavachalcone were the core components mediating the lipid-lowering activity of SLKDT polyphenols, with target proteins including TP53, STAT3, AKT1, HSP90AA1, and EGFR. This study elucidates the key components and critical targets underlying the lipid-lowering effects of SLKDT polyphenols, providing experimental evidence and theoretical support for the development of SLKDT-derived products and natural lipid-lowering agents.