广玉兰内酯抗脓毒症潜在靶点的筛选与鉴定

Screening and identification of potential anti-sepsis targets of magnograndiolide

目的 研究广玉兰内酯的分子特性,对其抗脓毒症的潜在靶点进行筛选并鉴定。方法 通过中药系统药理学分析平台(TCMSP)数据库分析广玉兰内酯的药理参数和分子特性;广玉兰内酯抗脓毒症靶点的确定,通过DRAR-CPI和Swiss Targetprediction软件筛选广玉兰内酯的潜在靶点,将OMIM、CTD以及TTD数据库中已被报道与脓毒症相关的疾病靶标进行匹配确定;通过分子对接软件鉴定广玉兰内酯抗脓毒症的潜在靶点,然后对潜在靶点进行作用通路分析。结果 广玉兰内酯成药性良好,其口服生物利用率为63.71%,药物相似度为0.19;在DRAR-CPI和Swiss Targetprediction软件中共筛选到150个潜在靶点,有9个与脓毒症相关的靶点,通过分子对接软件鉴定ELANE、S100A9、G6PD、ACE2、PTGS2和CASP3为广玉兰内酯抗脓毒症的潜在靶点,肿瘤坏死因子信号通路和5-羟色胺能突触为其作用通路。结论 广玉兰内酯可能通过ELANE、S100A9、G6PD、ACE2、PTGS2以及CASP3调控肿瘤坏死因子信号通路和5-羟色胺能突触起到缓解脓毒症的炎症作用,同时对脓毒症损伤的器官起到保护作用。

Objective To study the molecular characteristics of magnograndiolide, screen and identify its potential anti-sepsis targets. Methods The pharmacological parameters and molecular characteristics of magnograndiolide were analyzed by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). In terms of determining the anti-sepsis targets of magnograndiolide, the potential targets of magnograndiolide were screened by DRAR-CPI and SwissTargetprediction software, and the disease targets reported to be related to sepsis in OMIM, CTD and TTD databases were matched and determined. The potential anti-sepsis targets of magnograndiolide were identified by molecular docking software, and then the action pathway of the potential targets was analyzed. Results Magnograndiolide had good developability with the oral bioavailability of 63.71% and the drug similarity of 0.19. A total of150 potential targets were screened by DRAR-CPI and Swiss Targetprediction software, and 9 targets were related to sepsis. ELANE, S100A9, G6PD, ACE2, PTGS2 and CASP3 were identified as the potential anti-sepsis targets of magnograndiolide by molecular docking software. Tumor necrosis factor signaling pathway and serotonin synapse were the action pathways. Conclusion Magnograndiolide may regulate tumor necrosis factor signaling pathway and serotonin synapse through ELANE, S100A9, G6PD, ACE2, PTGS2 and CASP3, which can alleviate the inflammation of sepsis and protect the organs from injury caused by sepsis.