摘要
目的运用临床科研一体化模式,采用网络药理学、分子动力学模拟技术、代谢组学分析半夏泻心汤治疗艾滋病口腔病损的作用机制。方法使用中药系统药理学数据库与分析平台(TCMSP)数据库分析中药辅助治疗艾滋病口腔病损的核心中药所包含的活性化合物,构建活性成分-靶点基因网络图及核心靶点蛋白质-蛋白质相互作用(PPI)网络图,采用基因本体论(GO)富集和京都基因与基因组百科全书(KEGG)信号通路富集分析,分子对接技术进行验证,使用GROMACS 2023.2进行分子动力学模拟,评价复合体的稳定性。结果获得203个中药化合物和226个核心靶点,富集在215条信号通路上,主要为PI3K-Akt signaling pathway和Kaposi sarcoma-associated herpesvirus infection信号通路,筛选出4个主要活性化合物均能与AKT1、JUN等靶点蛋白结合,且结合能在-5.53 kcal/mol~-7.82kcal/mol,分子动力学模拟进一步验证豆甾醇-AKT1复合体结合稳定。109个差异代谢产物与显著基因主要参与7条代谢路径,为嘌呤代谢、色氨酸代谢、酪氨酸代谢等。结论半夏泻心汤主要通过嘌呤代谢、色氨酸代谢、酪氨酸代谢等代谢途径抑制炎症、降低病毒感染、提高免疫等功效达到治疗目的。
Objective To apply a clinical research integration model to retrospectively analyze the mechanism of Banxia Xiexin Decoction in treating oral lesions in acquired immune deficiency syndrome(AIDS)using network pharmacology,molecular dynamics simulation,and metabolomics techniques.The therapeutic mechanism provides a basis for the adjuvant treatment of oral lesions of AIDS with traditional Chinese medicine.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to analyze the active compounds contained in the core traditional Chinese medicine used to assist in the treatment of oral lesions of AIDS,and the active component target gene network map,core target protein protein interaction(PPl)network map,Gene Ontology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis were constructed and validated using molecular docking technology.GROMACS 2023.2 was used for the molecular dynamics simulations to evaluate the composite stability.Results In total,203 compounds and 226 core target genes were obtained,enriched in 215 signaling pathways,mainly the PI3K-Akt signaling pathway,and Kaposi sarcoma associated herpesvirus infection was screened,and four main active compounds were identified,all of which can interact with AKT1 and JUN,with binding energies ranging from-5.53 kcal/mol to-7.82 kcal/mol.Molecular dynamics simulations further confirmed the stability of the soybean sterol-AKT1 complex.Additionally,109 differential metabolites were involved in seven metabolic pathways,including purine,tryptophan,and tyrosine metabolism.Conclusions Banxia Xiexin Decoction achieves its therapeutic effects mainly through metabolic pathways such as purine,tryptophan,and tyrosine metabolism,inhibiting inflammation,reducing viral infection,and enhancing immunity.
作者
王一瑞
张鹏葛
古丽扎尔·阿布拉
邓江玲
戴璐
宋玉霞
WANG Yirui;ZHANG Pengge;Gulizhaer-Abula;DENG Jiangling;DAI Lu;SONG Yuxia(The Sixth People's Hospital of Xinjiang Uygur Autonomous Region,Urumgi 830013,Xinjiang,China)
出处
《中国艾滋病性病》
北大核心
2025年第11期1240-1246,共7页
Chinese Journal of Aids & STD
基金
新疆维吾尔自治区医药卫生天山英才项目(编号:TSYC202301A060)。
关键词
艾滋病
中药
网络药理学
代谢组学
分子动力学模拟
半夏泻心汤
AIDS
traditional Chinese medicine
network pharmacology
metabolomics technique
molecular dynamics simulation
Banxia Xiexin Decoction
