Luo Yin-Zhen, Zhao Bo-Wen, Chen Xi, Gu Yu, Zhang Yan-Ling
State Laboratory of Traditional Chinese Medicine Information Engineering, State Administration of Traditional Chinese Medicine, School of Chinese Material Medica, Beijing University of Chinese Medicine Beijing 100102, China.
Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(7):1436-1441. doi: 10.19540/j.cnki.cjcmm.20190111.004.
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.
动脉粥样硬化是中风的主要原因，而血脂异常是动脉粥样硬化最重要的危险因素。本文利用8个关键降脂靶点（即NPC1 L1、HMG-CoA还原酶、鲨烯合酶、微粒体甘油三酯转移蛋白、胆固醇酯转运蛋白、过氧化物酶体增殖物激活受体α、肝X受体α和肝X受体β）的药效团和分子对接模型，对由稀涎通栓制剂中13味中药材成分组成的中药小分子数据库进行筛选。筛选结果表明，该制剂可通过四组潜在活性化合物，即桃仁中的普鲁泊辛A、天麻中的天麻苷元A、川芎中的柠檬素-β-D-葡萄糖苷、半夏中的2'-（2,3-二羟基苯甲酰基）-獐牙菜苷和三七中的槲皮苷、天麻中的4-叔丁基-2-[(5-叔丁基-2-羟基苯基)甲氧基甲基]-6-(羟甲基)苯酚，对靶点NPC1 L1、HMG-CoA还原酶、肝X受体β和鲨烯合酶发挥调节血脂的作用。此外，最具潜在活性化合物的性质和提取工艺与稀涎通栓胶囊的制备工艺相符，这表明在稀涎通栓制剂现有的两种剂型中，胶囊剂比丸剂具有更多优势。本研究分析了稀涎通栓胶囊调节血脂治疗中风的药效学基础及作用机制，为其进一步研究和临床应用提供了依据。
