去甲汉黄芩素抗脓毒症潜在靶点的筛选与鉴定

Optimization and identification of potential target of norwogonin against sepsis

目的对去甲汉黄芩素的分子特征进行研究,筛选并鉴定其在治疗脓毒症的潜在靶点。方法基于中药系统药理学数据库与分析平台(TCMSP),对去甲汉黄芩素的药理参数以及分子特征进行分析;利用Swiss TargetPrediction和DRAR-CPI,甄别得到去甲汉黄芩素抗脓毒症的潜在目标靶点。去甲汉黄芩素的靶点筛选是基于人类孟德尔遗传病数据库,毒性与基因比较数据库和药物靶点数据库中收载的靶点相匹配得出。将筛选出的去甲汉黄芩素抗脓毒症的靶点,通过分子对接软件进一步筛选鉴定得到去甲汉黄芩素的潜在靶点。结果去甲汉黄芩素成药性良好,其口服生物利用度(OB)为39.40%,药物的相似度(DL)为0.21。实验筛选得到的105个潜在靶点中,发现其中有7个与脓毒症直接相关,在经分子对接软件鉴定后得出去甲汉黄芩素抗脓毒症的5个潜在靶点:凝血因子Ⅸ(F9)、人雌激素受体β(ESR2)、组织蛋白酶G(CTSG)、嘌呤核苷磷酸化酶(PNP)、丝裂原活化蛋白激酶1(MAPK1)。结论去甲汉黄芩素可通过与筛选的靶标结合,调控凝血因子Ⅸ参与凝血系统级联反应,调节ESR2维持雌激素水平的稳定,调节组织蛋白酶G、丝裂原活化蛋白激酶1和嘌呤核苷磷酸化酶抑制脓毒症组织和器官损伤,起到保护脓毒症损伤器官的作用,最终通过缓解脓毒症的症状及炎症等水平起到抗脓毒症作用。

Objective To optimize and identify the potential targets of norwogonin against sepsis by studying the characteristics of norwogonin.Methods The pharmacological parameters and molecular properties of baicalein were analyzed based on TCMSP(Pharmacological Database and Analysis Platform of Chinese Materia Medica System).To identify the potential target of anti-sepsis of baicalin,we use two important software,Swiss TargetPrediction and DRAR-CPI,The target selection of nobaicalein was based on the OMIM,the CTD and the TTD.After screening the anti-sepsis targets of baicalein,the potential targets of baicalein were further identified by molecular docking software.Results The oral bioavailability of was 39.40%and the drug-likeness was 0.21 indicating that norwogonin shows good drug formation.A total of 105 potential targets were screened through Swiss TargetPrediction and DRAR-CPI software,seven targets were directly related to sepsis.CTSG,ESR2,F9,PNP and MAPK1 were identified as the potential targets for anti-sepsis of norwogonin by molecular docking software.Conclusion Norwogonin can combine with the selected targets to regulate F9 involved in the cascade reaction of coagulation system,regulate ESR2 to maintain the stability of estrogen level,and regulate CTSG,MAPK1 and PNP to protect organs damaged induced by sepsis,finally prevent and treat sepsis.