【目的】 运用网络药理学与分子对接技术，探讨解肌透疹方干预基孔肯雅热的作用机制。【方法】 通过TCMSP数据库获 取解肌透疹方活性成分及其对应的作用靶标；从 GeneCards、OMIM、GEO数据库收集基孔肯雅热疾病相关靶点；筛选解肌 透疹方与基孔肯雅热的交集靶点；借助网络可视化与数据分析工具Cytoscape构建“药物-成分-靶点”网络；通过蛋白质-蛋 白质互作（PPI）分析、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析揭示解肌透疹方治疗基孔肯雅热 的潜在机制；采用分子对接及分子动力学模拟验证解肌透疹方关键活性成分与基孔肯雅病毒（CHIKV）细胞受体基质重塑相 关蛋白8（MXRA8）的结合。【结果】 共筛选出解肌透疹方99个活性成分。获得解肌透疹方活性成分靶点与基孔肯雅热相关基因 的交集靶点78个，核心靶点包括AKT1、PTEN、HIF1A、MAPK3、PTGS2、MMP9等。KEGG富集分析显示30条显著信号通 路（P＜0.05）可能与解肌透疹方治疗基孔肯雅热有关，包括 VEGF信号通路、TNF信号通路、FoxO信号通路、HIF-1信号通 路等。分子对接表明，紫花前胡苷、荷包牡丹碱、芍药苷、辛夷脂素、木犀草素、槲皮素、芍药甙元酮、连翘苷、香豆醇、 藿香黃酮醇、连翘脂素、刺芒柄花素、芒柄花酮II、楝叶吴萸素B等与MXRA8蛋白均具有较强的结合活性。分子动力学模 拟进一步证明解肌透疹方中紫花前胡苷与 MXRA8 蛋白可以稳定结合。【结论】 解肌透疹方可能通过紫花前胡苷、荷包牡丹 碱、芍药苷、辛夷脂素、木犀草素等关键活性成分，作用于 AKT1、PTEN、HIF1A、MAPK3、PTGS2、MMP9 等核心靶点， 调节VEGF信号通路、TNF信号通路、FoxO信号通路、HIF-1信号通路等，发挥抗炎、恢复抗病毒免疫、改善免疫应答等作 用。分子对接和分子动力学模拟表明紫花前胡苷与MXRA8蛋白结合作用最强，可能通过靶向MXRA8蛋白、抑制病毒入侵， 进而发挥抗病毒作用。

Objective To investigate the mechanism of Jieji Touzhen Formula （JTZF） in intervening with chikungunya fever （CHIKF） using network pharmacology and molecular docking. Methods Active components of JTZF and their corresponding targets were retrieved from the TCMSP database. Disease-related targets for CHIKF were collected from GeneCards，OMIM，and GEO databases. Common targets between JTZF and CHIKF were identified. A “herb-component-target” network was constructed using Cytoscape software. Protein-protein interaction （PPI） analysis，Gene Ontology （GO） enrichment，and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed to elucidate the potential mechanisms of JTZF against CHIKF. Molecular docking and molecular dynamics （MD） simulations were employed to validate the binding between key active components of JTZF and the host cellular receptor for chikungunya virus （CHIKV），Matrix Remodeling-Associated Protein 8（MXRA8）. Results A total of 99 active components of JTZF were screened. Seventy-eight common targets were identified between JTZF active components and CHIKF-related genes. Core targets included AKT1，PTEN，HIF1A，MAPK3，PTGS2，and MMP9. KEGG enrichment analysis revealed 30 significantly enriched pathways （P＜0.05） potentially associated with JTZF’s therapeutic effect on CHIKF， including the VEGF signaling pathway，TNF signaling pathway，FoxO signaling pathway，and HIF-1 signaling pathway. Molecular docking demonstrated that several components，including nodakenin，dicentrine，paeoniflorin， fargesin， luteolin， quercetin， paeoniflorigenone， forsythiaside， coumaryl alcohol， pogostone， phillygenin， formononetin， Ononin Ⅱ ， and evodionol B， exhibited strong binding activity with the MXRA8 protein. MD simulations further confirmed a stable binding conformation between nodakenin （from JTZF） and the MXRA8 protein. Conclusion JTZF may exert anti-inflammatory effects，restore antiviral immunity，and modulate immune responses against CHIKF through key active components such as nodakenin，dicentrine，paeoniflorin，fargesin， and luteolin. These components likely act on core targets like AKT1，PTEN，HIF1A，MAPK3，PTGS2，and MMP9， and modulate multiple signaling pathways including VEGF， TNF， FoxO， and HIF-1. Molecular docking and MD simulations suggest that nodakenin has the strongest binding affinity for MXRA8，indicating a potential antiviral mechanism involving the inhibition of viral entry by targeting the MXRA8 receptor.

R285

国家中医药管理局项目（编号：GZY-KJS-2025-38）；广东省中医药管理局课题（编号：YJXM202501）