基于网络药理学的补中益气丸抗疲劳机制研究

目的：探讨补中益气丸发挥抗疲劳作用的主要活性成分和潜在的机制。方法：通过中药系统药理学数据库与分析平台（TCMSP）筛选补中益气丸中的活性成分，利用Swiss Target Prediction、Drugbank、Cytoscape 3.7.1、R语言等数据库及软件预测活性成分作用靶点和“疲劳”相关靶点、构建疾病-药物-有效成分-靶基因的互作网络和蛋白质-蛋白质相互作用（PPI）网络，并进行关键靶基因的基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析，最后通过设计动物实验探究补中益气丸的抗疲劳药效。结果：分析表明与补中益气丸抗疲劳相关的163个潜在活性成分作用于与疲劳相关的108个靶点和160条通路。进一步网络特征分析发现表现主要活性成分为黄酮类和甾醇类化合物，通过参与脂多糖应答、对原细菌分子的反应等生物过程，调控MAPK、PI3K-AKT、TNF等信号通路进而发挥抗疲劳作用。药效学试验结果提示补中益气丸可显著增强小鼠运动耐力，但无显著缓解体力疲劳的效果。结论：补中益气丸具有多成分-多靶点-多途径的抗疲劳特点，其活性成分作用于多个靶点蛋白，调控多个生物过程及信号通路，起到改善机体氧化应激反应，调控细胞功能等作用，但在调节机体能量代谢方面未有明显的富集效果及药效学试验结果。本研究为进一步开发抗疲劳功能产品及药品和临床应用提供理论指导，为探究补中益气丸抗疲劳作用机制提供新思路。

Mechanism of Anti-fatigue of Buzhong Yiqi Pills Based on Network Pharmacology

To explore the main active components and potential mechanism of Buzhong Yiqi Pills in anti-fatigue.Methods:The potential active components in Buzhong Yiqi Pills were screened according to TCMSP database.Swiss target Prediction,drugbank,Cytoscape 3.7.1,R language and other databases and softwares were used to predict the target of active ingredients and fatigue related targets,to construct the interaction network of disease-drug-active-ingredients target genes and PPI network of protein interaction,and to carry out enrichment analysis of GO and KEGG of key target genes.Finally,animal experiments were designed to explore the anti-fatigue effect of Buzhong Yiqi Pills.Results:The results showed that 163 potential active components related to Buzhong Yiqi Pills could act on 108 targets and 160 pathways related to fatigue.Further analysis of the network characteristics showed that the main active components were flavonoids and sterols,which regulated MAPK,PI3K AKT,TNF and other signaling pathways through participating in lipopolysaccharide response,the reaction of source bacterial molecules and other biological processes,thus playing an anti-fatigue role.The results of pharmacodynamics test showed that Buzhong Yiqi Pills could significantly enhance the exercise endurance of mice,but had no significant effect on relieving physical fatigue.Conclusion:Buzhong Yiqi Pills gets the anti-fatigue characteristics of multi-component,multi-target and multi-channel.Its active components can regulate multiple biological processes and signal pathways by interacting with multiple target proteins,which can improve the body''s oxidative stress response and regulate cell function.However,it has no obvious enrichment effect and pharmacodynamic results in regulating the body''s energy metabolism.This study provides theoretical guidance for the further development of anti-fatigue functional products and drugs and clinical application,and provides new ideas for exploring the anti-fatigue mechanism of Buzhong Yiqi Pills.