基于网络药理学和分子对接技术探讨附子-白芍配伍治疗抑郁症的作用机制

Study on the Mechanism of Fuzi (Aconite) and Baishao (Paeoniae Radix Alba) Compatibility in the Treatment of Depression Based on Network Pharmacology and Molecular Docking Technology

目的:利用网络药理学方法和分子对接技术探讨附子-白芍配伍治疗抑郁症作用机制。方法:通过TCMSP和TCMID数据库筛选出附子和白芍的活性成分及相关靶点,使用DisGeNET、GeneCards等数据库筛选出抑郁症的潜在靶点,得到活性成分与疾病的交集靶点,以STRING数据库对活性靶点构建蛋白互作网络(PPI),使用R语言中CludterProfiler程序包进行GO功能及KEGG代谢通路分析;采用Cytoscape 3.7.2软件构建"药物-成分-靶点-通路"的相互作用网络图;通过Discovery Studio 2016软件对核心配体小分子和受体大分子进行分子对接分析。结果:筛选得到附子-白芍相关活性化合物6个,附子-白芍与抑郁症的共同靶点36个,网络图提示附子-白芍治疗抑郁症可能的有效化合物为三角豆素、β-谷甾醇、谷甾醇和Mairin,可能的靶点为PTGS1和PGR。GO功能富集分析筛选得生物学过程、细胞组成、分子功能分别为433条、58条及71条;KEGG富集筛选得神经活性配体-受体相互作用、5-羟色胺能突触、γ-氨基丁酸能突触及雌激素信号途径等67条信号通路;分子对接结果表明PGR与成分Mairin、β-谷甾醇和谷甾醇,PTGS1与三角豆素、β-谷甾醇均具有良好的亲和力。结论:附子-白芍配伍治疗抑郁症具有多靶点、多通路、多分子的特点,主要通过调节脑内神经递质(5-羟色胺、去甲肾上腺素和γ-氨基丁酸)等过程发挥抗抑郁的作用。

Objective: To explore the mechanism of Fuzi(Aconite) and Baishao(Paeoniae Radix Alba) in treating depression. Methods: The active ingredients and targets of Fuzi(Aconite) and Baishao(Paeoniae Radix Alba) were screened by TCMSP and TCMID platform. The potential targets of depression were screened by using GeneCards and DisGeNET, and other databases. The intersection targets of active components and diseases were obtained. The protein interaction network(PPI) of active targets was constructed by using STRING database. The GO function and KEGG metabolic pathway were analyzed by using the CludterProfiler package in R language.The interaction network diagram of "drug-component-target-pathway" was constructed by using Cytoscape 3.7.2 software. Moreover, the molecular docking analysis of core ligand small molecules and receptor macromolecules was carried out by using Discovery Studio 2016 software. Results: A total of 6 active compounds related to Fuzi(Aconite) and Baishao(Paeoniae Radix Alba) were screened, 36 common targets of Fuzi(Aconite)-Baishao(Paeoniae Radix Alba) and depression. The network diagram suggested that the effective compound of Fuzi(Aconite) and Baishao(Paeoniae Radix Alba) for depression is Deltoin, β-sitosterol, Sitosterol and Mairin, and PTGS1 and PGR were the possible targets. GO function enrichment analysis screened the biological process, cell composition, and molecular function to be 433, 58 and 71 respectively. KEGG enrichment screened 67 signal pathways including neuroactive ligand-receptor interaction, serotonergic synapse, γ-aminobutyric acid synapse and estrogen signal pathway. The results of molecular docking showed that PGR has good affinity with Mairin, β-sitosterol and Sitosterol, and PTGS1 has good affinity with Trichostatin and β-sitosterol. Conclusion: Fuzi(Aconite) and Baishao(Paeoniae Radix Alba) compatibility in the treatment of depression has the characteristics of multi-target, multi-channel and multi molecule. It plays an antidepressant role mainly through the regulation of brain neurotransmitters(5-hydroxytryptamine, norepinephrine and γ-aminobutyric acid).