Lipid regulation mechanism and dosage form selection of Xixian Tongshuan Preparation based on molecular simulation methods

Abstract

Atherosclerosis is the main cause of stroke, and dyslipidemia is the most important risk factor for atherosclerosis. In this paper, pharmacophore and molecular docking models of eight key lipid-lowering targets, namely NPC1 L1, HMG-CoA reductase, SQS, MTP, CETP, PPARα, LXRα and LXRβ, were used to screen out the small molecular database of traditional Chinese medicine(TCM), which was made up of ingredients of thirteen Chinese herbal medicines contained in Xixian Tongshuan Preparation. The screening results indicated that the preparation could showed an effect in regulating lipid on target NPC1 L1, HMG-CoA reductase, LXRβ and SQS through four groups of potential active compounds, namely prupersin A in peach kernel and suffruticoside A in gastrodiaelata, limocitrin-β-D-glucoside in Ligusticum chuanxiong, 2'-(2,3-dihydroxybenzoyl)-sweroside in Pinellia ternate and quercitrin in Panax notoginseng, 4-tert-butyl-2-[(5-tert-butyl-2-hydroxy-phenyl)methoxy-methyl]-6-(hydroxymethyl)phenol in Gastrodia elata. Moreover, the properties and extraction process of the most potentialactive compounds were consistent with the preparation process of Xixian Tongshuan Capsules, which indicated that the capsule had more advantages than the pill in the existing two dosage forms of Xixian Tongshuan Preparation. This study analyzed the pharmacodynamic basis and mechanism of Xixian Tongshuan Capsules in regulating lipid for treating stroke, and provided evidence for its further research and clinical application.