基于“从痰辨治”探讨石菖蒲治疗儿童注意缺陷多动障碍作用机制的网络药理研究

Network pharmacological study on the mechanism of Acorus tatarinowii in the treatment of ADHD from phlegm theory

目的基于“从痰辨治”的中医理论,运用网络药理学研究探讨石菖蒲治疗注意缺陷多动障碍(ADHD)的关键靶点及其作用机制。方法通过中药系统药理学数据库、分析平台(TCMSP数据库)及Genecards数据库筛选出石菖蒲的有效活性成分、潜在靶标,以及ADHD的疾病靶点;在R软件平台上筛选共同靶点,进行蛋白-蛋白相互作用(PPI)的网络构建、“药物-活性成分-靶点-疾病”的关系构建,进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析,使用pymol对对接结果进行可视化的处理。结果筛选出石菖蒲的9个活性成分及与ADHD相关的99个交集靶点;胰岛素(INS)、蛋白激酶1(AKT1)、Jun蛋白(JUN)、半胱氨酸蛋白酶3(CASP3)、Fos原癌基因(AP-1转录因子亚基,FOS)等靶蛋白是石菖蒲干预ADHD潜在靶点蛋白;相关靶点涉及多个生物过程与分子功能;石菖蒲治疗ADHD涤痰开窍的作用机制与细胞凋亡相关通路、炎症相关通路、脂类代谢信号通路、病毒感染通路等密切相关。结论石菖蒲的多种有效成分通过多条信号通路作用与不同靶点发挥作用,体现着中药多成分、多靶点、多环节、多途径的作用机制及特点,有助于探明石菖蒲治疗ADHD的作用机制。

Objective From the basic theory of traditional Chinese medicine based on"differentiated treatment from phlegm theory",the key target and mechanism of Acorus tatarinowii in the treatment of ADHD were discussed by means of network pharmacology.Methods The effective active components and potential targets of Acorus tatarinowii and disease targets of ADHD were screened by traditional Chinese medicine system pharmacology database,analysis platform(TCMSP database)and Genecards database.The common targets were screened on the R software platform;the protein-protein interaction(PPI)network was constructed;the"drug-active ingredient-target-disease"relationship was constructed;the GO and KEGG signal pathways were analyzed;pymol was used to visualize the docking results.Results Nine active components of Acorus tatarinowii and 99 intersection targets related to ADHD were screened out.Target proteins such as INS,AKT1,JUN,CASP3 and FOS were potential targets for intervention of ADHD by Acorus tatarinowii.The related targets involved multiple biological processes and molecular functions.The mechanism of Acorus tatarinowii in the treatment of ADHD was closely related to apoptosis-related pathways,inflammation-related pathways,lipid metabolic signal pathways,virus infection pathways and so on.Conclusion A variety of effective components of Acorus tatarinowii play a role through multiple signal pathways and different targets,reflecting the action mechanism and characteristics of multi-components,multi-targets,multi-links and multi-pathways of traditional Chinese medicine,which is helpful to explore the mechanism of Acorus tatarinowii in the treatment of ADHD.