title: The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and Its Molecular Mechanism.
abstract: This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique. According to the results, alisol acetates significantly lower the TC, TG, and LDL-C concentrations of hyperlipidemic mice, while raising HDL-C concentrations. Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion, bothin vivoandin vitro. Neither of these alisol acetates significantly lower the protein expression of HMG-CoA. This suggests that alisol acetates lower the TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug, which may exhibit an inhibition effect via directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group via molecular simulation.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Fei
authors.identifier: 0000-0003-0215-0312
authors.initials: F
authors.lastname: Xu
authors.affiliation: Jiangsu Hospital of Traditional Chinese Medicine (TCM), The First Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (TCM), Nanjing 210029, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu