基于网络药理学方法和分子对接技术探讨地榆-升麻药对治疗骨髓抑制的作用机制

Discussion on the mechanism of Diyu-Shengma couplet medicinals in the treatment of myelosuppression based on network pharmacology and molecular docking technology

目的:运用网络药理学方法和分子对接技术探讨“地榆-升麻”药对治疗骨髓抑制的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)获取“地榆-升麻”药对的有效成分并筛选相关的蛋白靶点,检索疾病基因库获得骨髓抑制的疾病靶点,交叉比较后识别潜在的治疗靶点。运用String数据库对蛋白质-蛋白质相互作用网络进行预测,筛选关键靶点。通过基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)功能富集分析,探索药对治疗疾病的生物学过程。通过分子对接技术对核心靶点和药物化合物进行验证,计算结合能,初步验证“地榆-升麻”药对治疗骨髓抑制的作用机制。结果:获得“地榆-升麻”药对有效成分8种和作用靶点174个,骨髓抑制疾病靶点502个,“地榆-升麻”药对与骨髓抑制的交集靶点50个,蛋白质-蛋白质相互作用网络结果确定了丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine-protein Kinase 1,AKT1)、肿瘤蛋白53(Tumor Protein 53,TP53)为核心靶点蛋白。GO功能分析得到功能模块2014个。KEGG通路富集分析得到信号通路136条。其中AKT1、TP53、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等核心靶点与骨髓抑制显著相关。本研究提示“地榆-升麻”药对通过“多成分-多靶点-多途径”发挥治疗骨髓抑制的作用。分子对接结果显示“地榆-升麻”药对主要化合物与核心靶点的结合紧密。结论:“地榆-升麻”药对治疗骨髓抑制可能通过化学致癌物受体的激活、脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化等信号通路,作用于AKT1、TP53、IL-6、TNF等靶点治疗骨髓抑制。此过程具有多成分、多靶点和多通路的特点。

Objective:To explore the mechanism of Diyu(Radix Sanguisorbae)-Shengma(Rhizoma Cimicifugae)in the treatment of myelosuppression by using network pharmacology and molecular docking.Methods:TCMSP database was used to obtain the active components of the Diyu-Shengma couplet medicinals and screen the related protein targets.Disease targets of myelosuppression were obtained by searching the disease gene bank,and potential therapeutic targets were identified after cross-comparison.Protein interaction network(PPI)was predicted by String database and key targets were screened.GO function analysis and KEGG function enrichment analysis were used to explore the biological process of couplet medicinals therapy.The core targets and drug compounds were verified by molecular docking technology,the binding energy was calculated,and the mechanism of Diyu-Shengma couplet medicinals in the treatment of myelosuppression was preliminatively verified.Results:A total of 8 active components and 174 action targets of Diyu-Shengma couplet medicinals were obtained,with 502 disease targets of myelosuppression disease were obtained,and 50 intersection targets of Diyu-Shengma couplet medicinals with myelosuppression were obtained.PPI results identified AKT1 and TP53 as the core target proteins.A total of 2014 GO functional modules were obtained by GO functional analysis,and 136 signaling pathways were obtained by KEGG pathway enrichment analysis,among which serine/threonine AKT1、TP53、IL-6、TNF as core targets were significantly correlated with myelosuppression.It is suggested that the Diyu-Shengma couplet medicinals can play a role in the treatment of myelosuppression through multi-component,multi-target and multi-pathway.The results of molecular docking showed that the binding of the main compound and the core target was close.Conclusion:The Diyu-Shengma couplet medicinals may act on Akt1,TP53,IL-6,TNF and other targets to treat myelosuppression through the activation of chemical carcinogen receptors,lipid and atherosclerosis,fluid shear stress,atherosclerosis and other signaling pathways.This process has the characteristics of multi-components,multi-targets and multi-pathways.