Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation.
Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation.
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DOI：
10.1038/s41598-022-13911-w
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发表时间：
2022-06-13
影响因子：
4.6
通讯作者：
Kang, Pinfang
中科院分区：
文献类型：
--
作者：
Tan, Xin;Xian, Wei;Li, Xiaorong;Chen, Yongfeng;Geng, Jiayi;Wang, Qiyi;Gao, Qin;Tang, Bi;Wang, Hongju;Kang, Pinfang
房颤是一种常见的房性心律失常，目前尚无特效治疗药物。Quercetin(QUE)已被用于治疗心律失常等心血管疾病。本研究运用网络药理学和分子对接的方法对Que在房颤中的作用机制进行了探讨。从PubChem中得到了Que的化学结构。应用TCMSP、Swiss Target Forecast、DrugBank、STITCH、Pharmmapper、CTD、GeneCards、DISGENET和TTD获取药物成分靶点和房颤相关基因，利用GEO数据库提取房颤和正常组织的差异表达基因。IL-6、VEGFA、Jun、MMP9和EGFR是治疗房颤的主要靶点，Que治疗房颤可能涉及AGE-RAGE信号通路、MAPK信号通路和IL-17信号通路在糖尿病并发症中的作用。分子对接显示QUE与关键靶点结合强烈，在房颤中有差异表达。体内实验结果表明，QUE可明显缩短房颤持续时间，改善心房重构，减少p-MAPK蛋白表达，抑制房颤的进展。将网络药理学和分子对接方法与体内研究相结合，加深了我们对槲皮素密集作用机制的理解，为临床房颤的治疗提供了靶向依据。
Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.
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