基于网络药理学及分子对接探究四黄止痢复方治疗仔猪腹泻的作用机制

doi:10.16431/j.cnki.1671-7236.2024.03.043

摘要/Abstract

摘要： 【目的】利用网络药理学方法探究四黄止痢复方治疗仔猪腹泻的作用机制并进行分子对接模拟验证。【方法】在TCMSP数据库收集黄芩、黄柏、大黄、黄连、板蓝根和甘草的活性成分及对应靶点,在GeneCards数据库收集仔猪腹泻相关靶点,并通过UniProt数据库对收集到的靶点进行标准化。通过Venn在线作图网站获得共有靶点,并使用Cytoscape 3.9.1制作药物-靶点网络图得到主要活性成分。对共有靶点进行蛋白互作(protein-protein interaction,PPI)、GO功能和KEGG通路富集分析,制作PPI网络图,筛选出核心靶点。利用PubChem和PDB数据库分析主要活性成分及靶点的3D结构文件,并通过Discovery Studio 2019 Client软件进行分子对接。【结果】四黄止痢复方治疗仔猪腹泻的主要活性成分为汉黄芩素、β-谷甾醇、金合欢素、去氢丹参酮ⅡA和四氢小檗碱,核心靶点包括肿瘤坏死因子(tumor necrosis factor,TNF)、胱天蛋白酶3(caspase-3,CASP3)、白细胞介素-6(interleukin-6,IL6)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)和转录激活因子3(signal transducer and activator of transcription 3,STAT3)。GO功能富集分析结果显示,四黄止痢复方主要作用靶点的生物学功能富集到RNA聚合酶Ⅱ启动子转录调控、细胞凋亡、血管生成、IL8产生、细胞因子活性、生长因子活性等条目。KEGG通路富集分析结果显示,四黄止痢复方主要作用靶点富集在信号转导、免疫系统、病毒性感染等相关分子信号通路。分子对接结果表明,汉黄芩素与TNF,去氢丹参酮ⅡA、四氢小檗碱和金合欢素与STAT3都显示出良好对接活性。【结论】四黄止痢复方可能通过汉黄芩素、β-谷甾醇、金合欢素、去氢丹参酮ⅡA和四氢小檗碱等主要活性成分作用于IL6、VEGFA、STAT3、TNF、CASP3等靶点,进而通过癌症通路、脂质与粥样动脉硬化和人巨细胞病毒感染等通路对仔猪腹泻起到抗炎、抗氧化等治疗效果,体现了中药的多成分、多靶点、多通路的特点。

关键词: 四黄止痢复方; 网络药理学; 分子对接; 仔猪腹泻; 作用机制

Abstract: 【Objective】 The aim of this study was to investigate the mechanism of action of Sihuang antidiarrheal granules in the treatment of piglets diarrhea basing on network pharmacology and molecular docking techniques.【Method】 The active ingredients and corresponding targets of Scutellaria baicalensis,phellodendron,rhubarb,coptis,licorice and isatis root were collected in the TCMSP database.The targets related to piglets diarrhea were collected from the GeneCards database.The collected targets were standardized by the UniProt database.Shared targets were obtained through Venn online mapping site.Cytoscape 3.9.1 was used to create a drug target network diagram to obtain the main active ingredients.Protein-protein interactions (PPI),GO function and KEGG pathways analysis were performed on the shared targets to produce the PPI network diagram and obtain the core targets.3D structure files of the main active ingredients and targets were obtained from PubChem and PDB databases.Molecular docking was performed by Discovery Studio 2019 Client software.【Result】 The main active ingredients of Sihuang antidiarrheal granules were wogonin,β-sitosterol,acaciain,dehydrotanshinone ⅡA and (R)-canadine.The core targets are caspase 3(CASP3),tumor necrosis factor (TNF),interleukin-6 (IL6),vascular endothelial growth factor A (VEGFA) and signal transducer and activator of transcription 3 (STAT3).The results of GO function analysis indicated that the biological functions of the main targets of action of Sihuang antidiarrheal granules were enriched to the entries of RNA polymerase Ⅱ promoter transcriptional regulation,apoptosis,angiogenesis,IL8 production,cytokine activity,and growth factor activity.The results of KEGG pathway analysis showed that the main targets of the action of Sihuang antidiarrheal granules were enriched in signal transduction,immune system,viral infection and other related molecular signaling pathways.The molecular docking results showed that wogonin with TNF,acaciain,dehydrotanshinone ⅡA and (R)-canadine with STAT3 showed good docking activity.【Conclusion】 Sihuang antidiarrheal granules might act on the targets of IL6,VEGFA,STAT3,TNF and CASP3 through the main active ingredients such as wogonin,β-sitosterol,acaciain,dehydrotanshinone ⅡA and (R)-canadine.In this way,it could have anti-inflammatory and antioxidant effects on piglet diarrhea through the pathways in cancer,lipid and atherosclerosis,and human cytomegalovirus infection,reflecting the multi-component,multi-target and multi-pathway characteristics of traditional Chinese medicine.

Key words: Sihuang antidiarrheal granules; network pharmacology; molecular docking; piglets diarrhea; mechanism

中图分类号:

S859.7

蒋秉妤, 陈宁, 崔亚男, 朱凯晴, 姜朋欣, 王旭涛, 李妍. 基于网络药理学及分子对接探究四黄止痢复方治疗仔猪腹泻的作用机制[J]. 中国畜牧兽医, 2024, 51(3): 1308-1319.

JIANG Bingyu, CHEN Ning, CUI Yanan, ZHU Kaiqing, JIANG Pengxin, WANG Xutao, LI Yan. Investigation of the Mechanism of Sihuang Antidiarrheal Granules in the Treatment of Piglets Diarrhea Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(3): 1308-1319.

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