Hypolipidemic Effect of Chloroform Extract of Lagenaria siceraria: Potential Inhibitory Activity of Phytochemicals Targeting the HMG-CoA Reductase Revealed by Molecular Docking and Simulation Studies

IF 2.8 4区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Qudsia Kanwal, Mahmood Ahmed, Atiq Ur-Rehman, Aneela Anwar, Samiah Shahid, Atif Shahzad, Attaullah Shah Bukhari, Muhammad Ahmad, Numan Yousaf, Muhammad Muddassar
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Abstract

Conventional systems of medicine play a crucial role in maintaining healthcare. Herbal medicines are intact and less harmful to human beings than synthetic medicines. This study aimed to investigate the phytochemicals and in vivo hypolipidemic effect of chloroform extract of Lagenaria siceraria in Triton X-100 (100 mg/kg body weight) induced hyperlipidemic Wistar rats. The phytochemical characterization and estimation were performed on the base of the GC-MS approach. The Lagenaria siceraria extract (250 and 500 mg/kg bw) was administered orally to hyperlipidemic-induced rats for 7 days to examine its hypolipidemic activity. The experimental animals did not display any acute toxicity. Atorvastatin (10 mg/kg bw) was used as a standard drug. Administration of Lagenaria siceraria extract lowers the total cholesterol (TC), triglyceride (TG), and low-density lipoproteins-cholesterol (LDL-C) levels whereas elevating the high-density lipoproteins-cholesterol (HDL-C) level. Histological studies of the liver and heart also showed the hypolipidemic effect of the extract. On the 8th day, no inflammation of the liver, myocardial necrosis, fibrosis, or atypia was seen. Furthermore, binding affinity and plausible binding mode of stigmastan-3-ol with HMG-CoA reductase were predicted by molecular docking studies which showed the same interaction patterns as atorvastatin. Moreover, the docking results were refined by 100 ns MD simulations which revealed that stigmastan-3-ol extract formed a stable complex with protein and did not induce any conformational changes in protein structure.
千层塔氯仿提取物的降血脂作用:分子对接和模拟研究揭示的针对 HMG-CoA 还原酶的植物化学物质的潜在抑制活性
传统医学体系在维护医疗保健方面发挥着至关重要的作用。与合成药物相比,中草药对人体的伤害更小,更完整。本研究旨在探讨氯仿提取物对 Triton X-100(100 毫克/千克体重)诱导的高脂血症 Wistar 大鼠的植物化学成分和体内降脂作用。植物化学成分的表征和估算是在气相色谱-质谱法的基础上进行的。对高脂血症诱导的大鼠进行为期 7 天的口服给药(250 毫克和 500 毫克/千克体重),以检测其降脂活性。实验动物未表现出任何急性毒性。阿托伐他汀(10 毫克/千克体重)被用作标准药物。服用川芎提取物可降低总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平,同时提高高密度脂蛋白胆固醇(HDL-C)水平。肝脏和心脏的组织学研究也显示了提取物的降脂作用。第 8 天,未发现肝脏炎症、心肌坏死、纤维化或非典型性。此外,通过分子对接研究预测了石杉碱甲-3-醇与 HMG-CoA 还原酶的结合亲和力和可能的结合模式,结果显示与阿托伐他汀的相互作用模式相同。此外,通过 100 ns MD 模拟对对接结果进行了改进,发现石杉碱甲-3-醇提取物与蛋白质形成了稳定的复合物,不会引起蛋白质结构的构象变化。
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来源期刊
Journal of Chemistry
Journal of Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
5.90
自引率
3.30%
发文量
345
审稿时长
16 weeks
期刊介绍: Journal of Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry.
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