Wang Ni, Chu Furui, Fei Changyi, Pan Lingyu, Wang Yongzhong, Chen Weidong, Peng Daiyin, Duan Xianchun, He Ling
Department of Pharmacy, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Front Pharmacol. 2022 May 20;13:809505. doi: 10.3389/fphar.2022.809505. eCollection 2022.
The mechanism of action of Naoluo Xintong decoction (NLXTD) for the treatment of ischemic stroke (IS) is unknown. We used network analysis and molecular docking techniques to verify the potential mechanism of action of NLXTD in treating IS. The main active components of NLXTD were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and IS targets were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Drugbank databases; their intersection was taken. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed and used to build protein-protein interaction networks. AutoDock Vina software was used for molecular docking, and animal experiments were conducted to verify the results. Hematoxylin and eosin staining was used to observe the brain morphology of rats in each group, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of relative mRNA in the brain tissue of rats. Western blot was used to detect the expression level of relative protein in the brain tissue of rats. Network analysis and molecular docking results showed that CASP3, NOS3, VEGFA, TNF, PTGS2, and TP53 are important potential targets for NLXTD in the treatment of IS. RT-qPCR and western blot results showed that NLXTD inhibited the expression of CASP3, TNF, PTGS2, and TP53 and promoted the expression of VEGFA and NOS3. NLXTD treats IS by modulating pathways and targets associated with inflammation and apoptosis in a multicomponent, multitarget manner.
脑络欣通汤（NLXTD）治疗缺血性脑卒中（IS）的作用机制尚不清楚。我们运用网络分析和分子对接技术来验证NLXTD治疗IS的潜在作用机制。NLXTD的主要活性成分从中药系统药理学（TCMSP）数据库中获取，IS的靶点从《人类孟德尔遗传在线》（OMIM）、GeneCards和DrugBank数据库中收集；取它们的交集。此外，进行了基因本体论和京都基因与基因组百科全书通路分析，并用于构建蛋白质-蛋白质相互作用网络。使用AutoDock Vina软件进行分子对接，并进行动物实验以验证结果。采用苏木精-伊红染色观察各组大鼠的脑形态，采用实时定量聚合酶链反应（RT-qPCR）检测大鼠脑组织中相对mRNA的表达水平。采用蛋白质印迹法检测大鼠脑组织中相对蛋白的表达水平。网络分析和分子对接结果表明，CASP3、NOS3、VEGFA、TNF、PTGS2和TP53是NLXTD治疗IS的重要潜在靶点。RT-qPCR和蛋白质印迹结果表明，NLXTD抑制了CASP3、TNF、PTGS2和TP53的表达，促进了VEGFA和NOS3的表达。NLXTD通过多成分、多靶点调节与炎症和凋亡相关的通路和靶点来治疗IS。
