摘要
目的本研究基于网络药理学方法探讨甘松的抗抑郁作用机制。方法NCBI、IMIM等主流药物研究数据库收集抑郁相关分子通路靶点,TCMSP数据库筛选甘松生物-中医药的利用度(OB)≥30%且药物相似性≥0.15的活性成分,通过Swiss Target Prediction、SEA等工具确定甘松活性成分与抑郁分子通路的交叉靶点,通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,根据中心性分析筛选出活性分子及核心靶点,进一步融合Gene Ontology和KEGG通路富集分析,揭示其潜在的分子机制。结果网络药理学分析显示,甘松药物活性分子中共筛选出槲皮素(Quercetin)、山柳醇(Betulin)、β-谷甾醇(Beta-sitosterol)等20个抗抑郁活性成分及193个潜在靶点,其中8个为共同作用的核心靶点。通过PPI网络分析,筛选出6个关键靶点(HTR2A、ADRA1B、GABRA1、SLC6A4、MAOA和DRD2)。GO富集分析显示这些靶点主要参与细胞增殖、凋亡和炎症反应等生物学过程。KEGG通路分析揭示了包括IL-6、TNF和NF-κB等重要通路在内的15条核心信号通路。分子对接结果表明,甘松中的槲皮素、木犀草素和甘草醇能够有效地与IL6(结合能量-9.4 kcal/mol)、TNF(结合能量-8.7 kcal/mol)和NFKB1(结合能量-8.3 kcal/mol)结合,提示这些活性成分可能通过调节炎症和免疫相关通路发挥抗抑郁作用。结论本研究通过分子对接验证甘松活性成分与核心靶点的结合能力,为甘松的抗抑郁作用提供理论依据。
Objective To explore the antidepressant mechanisms of Nardostachys jatamansi using network pharmacology approaches.Methods Depression-related molecular pathway targets were collected from mainstream drug research databases such as NCBI and IMIM.Active components of Nardostachys jatamansi,oral bioavailability(OB)≥30%and drug-likeness≥0.15,were selected from the TCMSP database.Intersection targets of active components and depression molecular pathways were identified using tools like Swiss Target Prediction and SEA.Protein-protein interaction(PPI)networks were constructed using the STRING database.Active molecules and core targets were chosen based on centrality analysis and further integrated with Gene Ontology(GO)and KEGG pathway enrichment analyses to reveal potential molecular mechanisms.Results According to network pharmacology analysis,a total of 20 antidepressant active components,including Quercetin,Betulin,Beta-sitosterol,and 193 potential targets,out of which 8 were found to be cooperative core targets,were screened out.Six key targets(HTR2A,ADRA1B,GABRA1,SLC6A4,MAOA,and DRD2)were identified through PPI network analysis.GO enrichment analysis showed these targets mainly involved in biological processes such as cell proliferation,apoptosis,and inflammatory response.KEGG pathway analysis unveiled 15 core signaling pathways,including critical pathways like IL-6,TNF,and NF-κB.Molecular docking results suggested that Quercetin,Betulin,and Beta-sitosterol from Nardostachys jatamansi could efficiently bind with IL6(binding energy-9.4 kcal/mol),TNF(binding energy-8.7 kcal/mol),and NFKB1(binding energy-8.3 kcal/mol),implying these active components might exert antidepressant effects by modulating inflammation and immunity-related pathways.Conclusions This study verifies the binding ability of Nardostachys jatamansi active components with core targets through molecular docking,providing theoretical groundwork for the antidepressant effects of Nardostachys jatamansi.
作者
张郝男
林鹏程
Zhang Haonan;Lin Pengcheng(School of Pharmacy,Qinghai Minzu University,Xining,Qinghai 810007,China;Qinghai Provincial Key Laboratory of Plant Chemistry on the Qinghai-Tibet Plateau,Xining,Qinghai 810007,China;Key Laboratory of Tibetan Medicine Resource Protection and Development on the Qinghai Tibet Plateau,State Ethnic Affairs Commission,Xining,Qinghai 810007,China)
出处
《齐齐哈尔医学院学报》
2025年第8期707-713,共7页
Journal of Qiqihar Medical University
基金
青海省科技计划(2024-SF-131)。
关键词
甘松
抗抑郁作用
网络药理学
蛋白质-蛋白质相互作用
GO富集分析
KEGG通路分析
Nardostachys jatamansi
Antidepressant effects
Network pharmacology
Protein-protein interaction
GO enrichment analysis
KEGG pathway analysis
