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积雪草苷对糖尿病大鼠的抗糖尿病和抗高脂血症活性、HMG CoA的作用:体内和计算机模拟方法

Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches.

作者信息

Ramachandran Vinayagam, Saravanan Ramalingam, Senthilraja Poomalai

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, India.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, India.

出版信息

Phytomedicine. 2014 Feb 15;21(3):225-32. doi: 10.1016/j.phymed.2013.08.027. Epub 2013 Sep 24.

DOI:10.1016/j.phymed.2013.08.027
PMID:24075211
Abstract

Hyperlipidemia is an associated complication of diabetes and also a major risk factor for cardiovascular diseases. The present study was designed to examine the antihyperlipidemic effect of asiatic acid (AA) in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Diabetic rats show increased plasma glucose, total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density liprotein, atherogenic index and decreased insulin and high density lipoprotein in diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly in contrast to the activities of lipoprotein lipase and lecithin cholesterol acyltransferase. In addition, the molecular docking of AA against HMG CoA reductase involved in cholesterol biosynthesis using Argus software. Diabetic rats were treated with AA shifted all these parameters towards normalcy. AA has shown best ligand binding energy 11.8122 kcal/mol. The antihyperlipidemic effect of AA was compared with glibenclamide; a well-known antihyperglycemic drug. In conclusion, this study indicates that AA showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes.

摘要

高脂血症是糖尿病的一种相关并发症,也是心血管疾病的主要危险因素。本研究旨在检测积雪草苷(AA)对链脲佐菌素(STZ)诱导的糖尿病大鼠的降血脂作用。通过单次腹腔注射STZ(40mg/kg体重)诱导雄性Wistar大鼠患糖尿病。糖尿病大鼠的血糖、总胆固醇、甘油三酯、游离脂肪酸、磷脂、低密度脂蛋白、极低密度脂蛋白、动脉粥样硬化指数升高,胰岛素和高密度脂蛋白降低。与脂蛋白脂肪酶和卵磷脂胆固醇酰基转移酶的活性相比,3-羟基-3-甲基戊二酰辅酶A(HMG CoA)还原酶的活性显著增加。此外,使用阿格斯软件对参与胆固醇生物合成的HMG CoA还原酶进行了AA的分子对接。用AA治疗的糖尿病大鼠使所有这些参数恢复正常。AA显示出最佳配体结合能11.8122千卡/摩尔。将AA的降血脂作用与格列本脲(一种著名的降糖药物)进行了比较。总之,本研究表明,AA在实验性糖尿病中除具有抗糖尿病作用外,还具有降血脂作用。

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