[关键词]
[摘要]
目的 采用网络药理学和分子对接技术探索姜黄素在抗艾滋病毒感染和艾滋病中的潜在作用机制,并通过体外实验验证其抗病毒活性。方法 使用PubChem、TCMSP等数据库预测姜黄素的潜在靶点。利用DisGeNET等数据库确定艾滋病疾病靶点。通过交集分析确定共同靶点,并构建蛋白质相互作用(PPI)网络,筛选核心靶点。通过Cytoscape软件和Metascape平台进行网络拓扑学分析、基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。使用Autodock Vina软件评估姜黄素与关键靶点的结合潜力。通过细胞计数试剂盒-8(CCK-8)试验评估姜黄素的细胞毒性,HIV假病毒实验检测姜黄素的抗病毒效果,qRT-PCR和Western blotting分析主要基因盒蛋白表达变化。结果 姜黄素作用靶点与艾滋病疾病相关靶点的交集共有307个交集靶点。PPI网络分析发现53个核心靶点。GO富集分析结果显示,姜黄素抗艾滋病主要涉及的生物学过程有对激素的响应、对肽的响应等。KEGG信号通路富集分析发现关键信号通路包括丝裂原活化蛋白激酶(MAPK)信号通路,磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等。分子对接分析显示姜黄素与白蛋白(ALB)、表皮生长因子受体(EGFR)、Akt1等关键靶点具有强结合能力。HIV假病毒实验显示姜黄素能显著降低病毒感染率。qRT-PCR和Western blotting结果显示姜黄素处理后EGFR表达降低。结论 姜黄素通过作用于多个与HIV相关的靶点显示出抗HIV的潜力,其多靶点作用机制为艾滋病治疗提供了新的可能性。
[Key word]
[Abstract]
Objective To explore the potential mechanisms of curcumin against HIV infection and acquired immune deficiency syndrome by network pharmacology and molecular docking techniques, followed by in vitro experimental validation of its antiviral activity. Methods Potential targets of curcumin were predicted using databases such as PubChem and TCMSP. Acquired immune deficiency syndrome-related targets were identified using DisGeNET databases. Common targets were determined through intersection analysis, and a PPI network was constructed to screen core targets. GO function enrichment, and KEGG pathway enrichment were performed using Cytoscape software and the Metascape platform. Autodock Vina software was used to evaluate the binding affinity of curcumin with key targets. The cytotoxicity of curcumin was assessed using the CCK-8 assay, its antiviral effect was detected by HIV pseudovirus assay, and changes in major gene expression were analyzed by qRT-PCR and Western blotting. Results A total of 307 overlapping targets were identified between curcumin targets and acquired immune deficiency syndrome-related targets. PPI network analysis revealed 53 core targets. GO enrichment analysis indicated that the biological processes primarily involved in the anti-acquired immune deficiency syndrome effect of curcumin included response to hormone and response to peptide. KEGG pathway enrichment analysis identified key signaling pathways, including the MAPK and the PI3K/Akt signaling pathway. Molecular docking analysis showed strong binding affinity of curcumin with key targets such as ALB, EGFR, and Akt1. The HIV pseudovirus assay demonstrated that curcumin significantly reduced viral infection rates. qRT-PCR and Western blotting results showed decreased EGFR expression following curcumin treatment. Conclusion Curcumin exhibits anti-HIV potential by acting on multiple HIV-related targets, and its multi-target mechanism offers new possibilities for acquired immune deficiency syndrome treatment.
[中图分类号]
R285.5;R286.6
[基金项目]
广东省中医药局科研项目(20232097,20251427);东莞市科技计划项目(20241600403291);广东医科大学临床+基础科技创新专项计划(4SG25302G)