白术中白术内酯Ⅰ、Ⅱ、Ⅲ的靶标预测及蛋白互作网络研究  

Study on Target Prediction and Protein-protein Interaction Networks of Atractylenolide Ⅰ,Ⅱ,Ⅲ in Atractylodes macrocephala

作　　者：刘志强 刘和波[2] 王博龙[1] LIU Zhiqiang;LIU Hebo;WANG Bolong(School of Chemical and Biological Engineering,Yichun University,Jiangxi Yichun 336000,China;School of Medicine,Yichun University,Jiangxi Yichun 336000,China)

机构地区：[1]宜春学院化学与生物工程学院,江西宜春336000 [2]宜春学院医学院,江西宜春336000

出　　处：《中国药房》2018年第23期3241-3246,共6页China Pharmacy

基　　金：江西省科技计划项目(No.20123BBG70259)

摘　　要：目的:探究白术中白术内酯Ⅰ、Ⅱ、Ⅲ的潜在靶标及药理机制,为白术内酯类药物的研究开发提供网络药理学理论线索。方法:利用药效团匹配靶标服务器PharmMapper虚拟筛选白术内酯Ⅰ、Ⅱ、Ⅲ的潜在靶标,借助STRING平台构建靶蛋白互作网络并筛选关键靶标,利用治疗靶标数据库探究靶标的功能以及与通路、疾病的关系,采用系统分子对接服务器SystemsDock将白术内酯Ⅰ、Ⅱ、Ⅲ与关键靶标进行分子对接,验证白术内酯Ⅰ、Ⅱ、Ⅲ与关键靶标的亲和活性。结果:白术内酯Ⅰ、Ⅱ、Ⅲ主要作用于丝裂原激活蛋白激酶(MAPK)8、半胱氨酸蛋白酶(CASP)3、过氧化物酶体增殖物激活受体(PPARG)、一氧化氮合酶(NOS)3、热休克蛋白(HSP)90AA1、雌激素受体(ESR)1、雄激素受体(AR)、糖原合成酶激酶(GSK)3B、骨形态发生蛋白(BMP)2、凝血酶原前体片段F2等10个关键靶标,具有治疗肿瘤、心血管疾病、中枢神经系统疾病的潜在药理活性;除白术内酯Ⅰ与MAPK8的亲和力小于4.25外,白术内酯Ⅰ、Ⅱ、Ⅲ与对应靶标对接分数基本都在4.25以上,均属于有效结合。结论:白术内酯Ⅰ、Ⅱ、Ⅲ具有"多靶点、多通路、多疾病"的药理作用机制。OBJECTIVE：To explore the potential target and pharmacological mechanism of atractylenolide Ⅰ,Ⅱ and Ⅲ in Atractylodes macrocephala,and to provide network pharmacology theoretical clues for further research and development of alicolactone. METHODS：The potential target of atractylenolide Ⅰ,Ⅱ and Ⅲ were screened by pharmacophore matching target server PharmMapper,and STRING platform was adopted to establish protein mutual network and screen key target. Therapeutic targets database was used to explore the function of the target and its relationship with pathways and diseases. Molecular docking server SystemsDock was used to dock the atractylenolide Ⅰ,Ⅱ,and Ⅲ with key targets to verify the affinity of atractylenolide Ⅰ, Ⅱ,and Ⅲ with key targets. RESULTS：Atractylenolide Ⅰ,Ⅱ,and Ⅲ mainly acted on 10 key targets such as MAPK8,CASP3, PPARG, NOS3, HSP90AA1, ESR1, AR, GSK3B, BMP2, prothrombin precursor fragment F2, showing potential pharmacological activity in the treatment of tumor,cardiovascular disease and central nervous system disease. Except that the affinity between atractylenolide Ⅰ and MAPK8 was less than 4.25,the docking scores of atractylenolide Ⅰ,Ⅱ,and Ⅲ with the corresponding target were basically above 4.25,and were valid. CONCLUSIONS：Atractylenolide Ⅰ ,Ⅱ ,and Ⅲ have the pharmacological mechanism of“multiple targets,multiple pathways,and multiple diseases”.

关 键 词：网络药理学 白术 白术内酯Ⅰ 白术内酯Ⅱ 白术内酯Ⅲ 靶点 通路 蛋白互作网络 

分 类 号：R285[医药卫生—中药学]