Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.
Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.
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DOI：
10.1155/2021/9965906
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发表时间：
2021
影响因子：
--
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Ye J;Li L;Hu Z
茵陈五苓散常用于临床治疗高脂血症，但其作用机制尚不清楚。本研究采用网络药理学、分子对接和分子动力学模拟相结合的方法，对茵陈五苓散中的有效成分进行研究，并探讨其治疗高脂血症的作用机制。 利用TCMSP数据库获得茵陈五苓散中的主要活性成分，利用NCBI和DisGeNet数据库获得高脂血症相关的主要靶基因，并利用EXCEL软件获得交叉靶点。利用Cytoscape 3.7.2软件构建“中药-活性成分-靶点”网络，利用STRING平台对交叉靶点进行“蛋白质-蛋白质互作”（PPI）分析。然后使用Bioconductor软件和RX 64 4.0.0软件对靶标进行GO功能富集分析和KEGG途径富集分析。使用AutoDock维纳软件模拟核心蛋白-配体相互作用的分子对接。利用Amber 18软件对分子对接得到的最佳核心蛋白-配体进行了分子动力学模拟。 茵陈五苓散中共检出63种有效成分，对应175个靶点，508个高脂血症靶点，55个交叉靶点。Cytoscape 3.7.2显示关键活性成分为槲皮素、异鼠李素、花旗松素、去甲氧基毛细血管素和阿替匹林A。PPI网络显示，涉及的关键蛋白是AKT 1，IL 6，VEGFA和PTGS 2。GO富集分析发现，基因富集主要是在响应氧气水平和营养水平的囊泡腔，并与膜筏。这些主要富集在AGE-E2（advanced glycation end products-receptor for advanced glycation end products）信号通路、糖尿病并发症、流体切应力、动脉粥样硬化等通路中。分子对接结果表明PTGS 2-槲皮素、PTGS 2-异鼠李素和PTGS 2-花旗松素之间具有关键结合活性。分子动力学模拟结果表明，PTGS 2-槲皮素、PTGS 2-异鼠李素和PTGS 2-花旗松素的结合更稳定，其结合自由能分别为PTGS 2-槲皮素-29.5 kcal/mol、PTGS 2-异鼠李素-32 kcal/mol和PTGS 2-花旗松素-32.9 kcal/mol。 本研究以网络药理学为基础，揭示茵陈五苓散治疗高脂血症的潜在分子机制。
Yinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed to investigate the active ingredients found in Yinchen Wuling powder and find its mechanism of action when treating hyperlipidemia, using a combination of network pharmacology, molecular docking, and molecular dynamics simulation approaches. The TCMSP database was used to obtain the principle active ingredients found in Yinchen Wuling powder and the NCBI and DisGeNet databases were used to obtain the main target genes involved in hyperlipidemia, and the intersectional targets were obtained by EXCEL. We also used Cytoscape 3.7.2 software to construct a “Traditional Chinese Medicine-Active Ingredient-Target” network and use STRING platform to conduct “protein-protein interactional” (PPI) analyses on the intersection targets. Bioconductor software and RX 64 4.0.0 software were then used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the targets. Molecular docking of core protein-ligand interactions was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal core protein-ligand obtained by molecular docking using Amber18 software. A total of 63 active ingredients were found in Yinchen Wuling powder, corresponding to 175 targets, 508 hyperlipidemia targets, and 55 intersection targets in total. Cytoscape 3.7.2 showed that the key active ingredients were quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, and artepillin A. The PPI network showed that the key proteins involved were AKT1, IL6, VEGFA, and PTGS2. GO enrichment analysis found that genes were enriched primarily in response to oxygen levels and nutrient levels of the vesicular lumen and were associated with membrane rafts. These were mainly enriched in AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis, as well as other pathways. The molecular docking results indicated key binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin. Results from molecular dynamics simulations showed that PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin bound more stably, and their binding free energies were PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 kcal/mol, and PTGS2-taxifolin -32.9 kcal/mol. This study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.
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影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
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作者：
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作者：
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