Anti-hypercholesterolemic effects of small-molecule pectin from Premna ligustroides Hemsl leaves: Modulation of inflammatory markers and gut microbiota in mice.

Small-molecule pectin (SMP) extracted from the leaves of Premna ligustroides Hemsl, with a molecular weight range of 5000-35,000 Da, has demonstrated anti-inflammatory and lipid-lowering properties in vitro. This study explored the effects of SMP on hypercholesterolemia in mice, with a focus on inflammation, lipid profiles, and cholesterol metabolism. Mice received SMP at doses of 607, 303, and 152 mg/kg body weight. Key biomarkers were assessed, including serum lipid levels, inflammatory factors in serum and liver, oxidative stress markers, short-chain fatty acids in cecal contents, cecal microbiota composition, and cholesterol metabolism-related gene expression. The results showed that SMP treatment normalized total cholesterol and alanine aminotransferase levels. In the medium-dose group, interleukin (IL)-1β and IL-18 levels decreased by 35.08 % and 29.90 %, respectively, compared to the model group. Serum malondialdehyde levels declined by 52.35 %, while superoxide dismutase levels increased by 18.48 %. Tumor necrosis factor-α and IL-6 levels were reduced by 44.13 % and 89.32 %, respectively. Additionally, SMP promoted the growth of beneficial bacteria, such as Muribaculum and Akkermansia, while suppressing harmful bacteria, including Acetatifactor. These microbiota changes were associated with elevated propionic acid levels and regulation of the CYP7A1/FXR/SREBP-2/LDLR signaling pathway. These findings underscore SMP's potential to improve cholesterol metabolism and mitigate inflammation, positioning it as a promising dietary intervention for the management of hypercholesterolemia.