The Cholesterol‐Lowering Effect of Alisol Acetates Based on HMG‐CoA Reductase and Its Molecular Mechanism
Fei Xu, Hui Yu, Lu Cai, Jun Chen, Wei Gu · Evidence-based Complementary and Alternative Medicine · 2016
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, both in vivo and in 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.