中国中医药信息杂志2024，Vol.31Issue(10)：31-38,8.DOI:10.19879/j.cnki.1005-5304.202403004
基于网络药理学、分子对接和动物实验探究柴胡疏肝散治疗抑郁症作用机制
Mechanism of Chaihu Shugan Powder in Treatment of Depression Based on Network Pharmacology,Molecular Docking and Experimental Verification
摘要
Abstract
Objective To predict the mechanism of Chaihu Shugan Powder against depression based on network pharmacology and molecular docking technology;To verify them through animal experiment of chronic unpredictable mild stress(CUMS)depression model rats.Methods TCMSP was used to screen the active components of Chaihu Shugan Powder and the related targets were obtained.Disease targets were retrieved by DisGeNET,GeneCards and GEO databases.The protein-protein interaction(PPI)network construction,GO and KEGG pathway enrichment analyses were conducted to determine the action pathway of Chaihu Shugan Powder against depression.Molecular docking of main active components and potential targets was performed.The depression model was established by CUMS combined with solitary rearing method,in which Chaihu Shugan Powder and PI3K specific inhibitor LY294002 were used to intervene depression model rats.Western blot and qPCR were respectively used to detect the action pathway related proteins and mRNAs.ELISA was used to detect the contents of monoamine neurotransmitters 5-HT and NE in hippocampal tissue,and their pathways of action were integrated and analyzed.Results Totally 118 active components of Chaihu Shugan Powder against depression and 74 potential targets were screened;KEGG pathway enrichment analysis indicated that action pathway of Chaihu Shugan Powder against depression were closely related to PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that quercetin,kaempferol,β-sitosterol,isorhamnetin,naringenin had good binding activity with AKT1,PIK3CA,GSK3B,IL6,IL1B.The animal experiments showed that Chaihu Shugan Powder could improve the depression-like behavior of model rats,increase the phosphorylation levels of PI3K and Akt in hippocampal tissue,down-regulate the expression of GSK3β,and increase the contents of 5-HT and NE.LY294002 could reverse the effect of Chaihu Shugan Powder.The results of integration analysis showed that PI3K/Akt signaling pathway of Chaihu Shugan Powder was closely related to metabolism of 5-HT and NE.Conclusion Chaihu Shugan Powder can exert antidepressant effects by activating the PI3K/Akt signaling pathway,inhibiting the expression of GSK3β,and increasing the levels of monoamine neurotransmitters 5-HT and NE.关键词
柴胡疏肝散/抑郁症/网络药理学/分子对接/作用机制/大鼠Key words
Chaihu Shugan Powder/depression/network pharmacology/molecular docking/mechanism/rats分类
医药卫生引用本文复制引用
滕海英,余宇燕,周小如,王玉露..基于网络药理学、分子对接和动物实验探究柴胡疏肝散治疗抑郁症作用机制[J].中国中医药信息杂志,2024,31(10):31-38,8.基金项目
福建省卫生健康科技计划项目(2020QNA070) （2020QNA070）
