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水飞蓟宾对 HMG-CoA 还原酶的抑制作用及其抗氧化潜能改善兔血脂异常和动脉粥样硬化斑块

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits.

机构信息

Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Department of Zoology, Jai Narain Vyas University, Jodhpur, Rajasthan, India.

出版信息

PLoS One. 2022 Mar 3;17(3):e0264646. doi: 10.1371/journal.pone.0264646. eCollection 2022.

Abstract

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

摘要

这项分配的工作旨在研究金合欢种子水提物的植物成分抑制 HMG-CoA 还原酶和动脉粥样硬化斑块消退的能力。采用 LC-MS/MS 评估了测试提取物的化学指纹图谱。随后,使用标准方案进行了体外、体内和计算机模拟分析。测试提取物的体外评估显示 HMG-CoA 还原酶抑制率为 74.1%。对测试提取物的体内评估表明,经治疗的高胆固醇血症兔的血脂生物标志物指标即致动脉粥样硬化指数、卡斯特利风险指数(I 和 II)、致动脉粥样硬化系数以及血脂谱显著改善(P≤0.001)。随后,动脉粥样硬化斑块和抗氧化水平显著降低。分子对接的计算机模拟研究显示,测试提取物的主要植物成分即二十烷酸、亚油酸和黄烷-3-醇与 HMG-CoA 还原酶的靶蛋白具有相互作用能力。显示出最高对接复合物的 RMSF 值和势能具有显著的相互作用。因此,自由能的溶剂化、相互作用角、回转半径和 SASA 显示出最高对接复合物的显著稳定性。综合结果数据表明,金合欢种子水提物的植物成分具有抑制 HMG-CoA 还原酶和提高抗氧化水平的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c707/8893677/6c553e681b2f/pone.0264646.g001.jpg

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