Modulation Mechanism of Proanthocyanidins from Leaves of Bayberry (Myrica rubra Sieb. Et Zucc.) on Hyperlipemic Rats Induced by High-fat-diet

Abstract

Aim: To investigate the lipid-lowering effect of proanthocyanidins from Bayberry leaf (BLP) in rat model of hyperlipidemia and to clarify the underlying molecular mechanism. Study Design: The study includes in-vitro and in-vivo experiments in rat model. Place and Duration of Study: College of Life Sciences, China Jiliang University, Zhejiang Province, China, between March 2021 to December 2021. Methodology: BLP were preliminarily characterized. The adsorption rate of BLP was determined based on in-vitro binding to bile acids. The effect of BLP on membrane transport of bile acids was examined through Caco-2 mono-layer in trans-well. The effect of BLP on serum enzyme activity and lipid metabolism genes expression were also investigated in a high-fat diet rat model. Results: Total poly-phenol and proanthocyanidins contents were 97.93% and 82.25% respectively, using gallic acid and Epigallocatechin-3-O-Gallate (EGCG) as equivalent. The total flavonoid content was 12.05% (quercetin as equivalent) and the average polymerization degree of BLP was determined as 4.51. And the in-vitro average binding rates of BLP to bile acids were all higher than 80%. Meanwhile, the membrane transport of bile acids in Caco-2 monolayer cells were significantly obstructed by BLP. Furthermore, the total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) concentrations in rat serum were markedly decreased after 28-day of BLP treatment. And the hepatic steatosis was significantly ameliorated in high-dose BLP treatment group compared with high fat group. High-dose administration of BLP significantly reduced the levels of 3-hydroxy-3-3methylglutary-CoA (HMG-CoA) reductase, while the levels of ATP binding cassette transporters (ABCG-5), liver X receptor-α (LXR-α) and cholesterol-7α-hydroxylase (CYP7A1) were significantly increased. Conclusion: BLP can mediate the serum lipid metabolism via preventing bile acids re-absorption, reducing oxidative stress and regulating the expression of lipid metabolism-related genes.