中国科学院心理健康重点实验室知识库

通过网络药理学结合分子对接技术研究蜘蛛香治疗创伤后应激障碍（post-traumatic stress disorder，PTSD）的有效成分及作用机制。利用文献挖掘获取蜘蛛香主要成分，SwissTargetPrediction，BATMAN及ETCM平台预测药物相关靶点，并通过DrugBank，TTD及CTD数据库搜集PTSD疾病相关基因；取药物-疾病交集基因再利用STRING构建蛋白互作（PPI）网络，根据拓扑学参数筛选蜘蛛香治疗PTSD的关键靶点；采用Cytoscape 3.7.2构建化合物-靶点网络。通过DAVID进行GO功能及KEGG通路富集分析。运用Cytoscape 3.7.2软件构建“成分-靶点-通路”网络，分析获取网络中的关键靶点与其对应成分，并利用分子对接进行初步验证。分析结果显示网络中包含蜘蛛香抗PTSD的有效成分缬草醚醛、二氢缬草素、缬草三酯、chlorovaltrate K、8-羟基松脂醇、6-hydroxyluteolin、芹菜素、金合欢素、香叶木素、木犀草素、山柰酚、山橘脂酸及广藿香醇等47个化合物，CNR1，MAOA，NR3C1，MAPK14，MAPK8，HTR2C及DRD2等94个靶点，GO功能富集分析得到29个GO条目（P＜0.05），KEGG通路富集得到20条信号通路（P＜0.05），主要涉及神经活性配体-受体相互作用、血清素能突触、钙信号通路、cAMP信号通路、多巴胺能突触、逆行内源性大麻素信号、神经营养蛋白信号通路、间隙连接、胆碱能突触、雌激素信号通路、谷氨酸能突触及长时程增强等信号通路。通过分子对接发现氢键、π-π作用和疏水作用可能是其主要作用的形式。该研究通过成分-靶点-通路网络以及分子对接技术，筛选蜘蛛香抗PTSD的有效成分，探究其抗PTSD的作用机制，为从中医药中发掘具有抗PTSD作用的药物并阐明其作用机制提供科学依据。

This paper aims to investigate the active components and mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder (PTSD) based on network pharmacology and molecular docking. The main components and targets of Valerianae Jatamansi Rhizoma et Radix were obtained by literature mining methods, SwissTargetPrediction, BATMAN and ETCM database. PTSD-related genes were collected from DrugBank, TTD and CTD databases. The proteinprotein interaction (PPI) network was constructed based on STRING, and the core targets of Valerianae Jatamansi Rhizoma et Radix in the treatment of PTSD were selected according to the topological parameters. Cytoscape 3.7.2 was used to construct the compound-target network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. The relationship network of “compound-target-pathway” was constructed through Cytoscape 3.7.2 to analyze and obtain the key targets and their corresponding components in the network, and their results were verified by molecular docking. The results showed that a total of 47 components (such as valeraldehyde, dihydrovalerin, valerate, chlorovaltrate K, 8-hydroxypinoresinol, 6-hydroxyluteolin, apigenin, farnesin, vanillin, luteolin, kaempferol, glycosmisic acid and pogostemon) of Valerianae Jatamansi Rhizoma et Radix may act on 94 key targets such as CNR1, MAOA, NR3C1, MAPK14, MAPK8, HTR2C and DRD2. Totally 29 GO terms were obtained by GO functional enrichment analysis (P<0.05), and 20 signal pathways were obtained from KEGG pathway enrichment, mainly involving neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling pathway, cAMP signaling pathway, dopaminergic synapse, retrograde endocannabinoid signaling, neurotrophin signaling pathway, gap junction, cholinergic synapse, estrogen signaling pathway, glutamatergic synapse and long-term potentiation. Molecular docking analysis showed that hydrogen bonding, hydrophobic effecting and π-π interaction maybe the main forms of interaction. This study used the network of compound -target-pathway and molecular docking technology to screen the effective components of Valerianae Jatamansi Rhizoma et Radix against PTSD, and explore its anti-PTSD mechanism, so as to provide scientific basis for exploring the anti -PTSD drugs from traditional Chinese medicine and clarifying its mechanism of action.

国家自然科学基金面上项目（81673560）;; 北京市技术开发类横向课题（2017110031015577）