抗高原反应中药红景天化学成分的潜在靶标研究  

Potential target of chemical constituents from the Rhodiola plants

作　　者：梁子亮[1] 张旭毅[1] 欧阳璞心 王藩[1] 刘海峰[1] 刘惠亮[1] LIANG Ziliang;ZHANG Xuyi;OUYANG Puxin;WANG Fan;LIU Haifeng;LIU Huiliang(Department of Medical Office, General Hospital of Chinese People's Armed Police Force, Beijing 100039, China)

机构地区：[1]武警总医院医疗科,北京100039

出　　处：《中华灾害救援医学》2017年第4期186-190,共5页Chinese Journal of Disaster Medicine

基　　金：首都医学发展专项(2014-2-5131);武警总医院院级课题(WZ2015008)

摘　　要：目的红景天作为抗高原反应的常用中药,其化学成分的作用靶标和机制一直未得到明确阐释,本研究从文献调研的187种红景天化学成分出发,针对缺氧诱导因子-1α(hypoxia-inducible factor 1α,HIF-1α)降解途径的10个靶标,利用Auto Dock Vina分子对接程序,对化学成分和靶标之间的相互作用进行研究。方法 (1)构建了187种化学成分数据库;(2)对靶标晶体结构进行复原测试,以均方根偏差(root-mean-square deviation,RMSD)进行评价,最终确定靶标蛋白对接参数,成功构建10个靶标信息的靶标数据库;(3)对化合物数据库的187个化合物与靶标数据库的10个靶标及其参数进行两两分子对接,得到排名前5%的化合物为阳性化合物,构建化合物-靶标相互作用网络图。结果红景天中的18种化学成分与3个以上的靶标有相互作用,验证了红景天多靶点作用的分子机制。结论在所筛选出的化合物中,化合物15(Rhodionin)、16(Rhodiosin)、26(Crenulatin)、56(Pharienside)和184(Pyridrde)是已报道的红景天的药理活性成分,本研究分别将其结构及对应作用靶标罗列出来,为红景天药理成分的靶标确定及后期研发提供参考。Objective Rhodiola is a commonly used drug for resistance to altitude sickness,however the target of its chemicalconstituents and mechanism of action have not been clearly explained.In this paper,187chemical constituents of Rhodiola were collectedthrough a literature review,AutoDock Vina,a molecular docking program,was used to predict the interaction between chemical constituentsand10identifiable targets of(hypoxia-inducible factor1α)HIF-1αdegradation pathway.Methods(1)A database comprising of the187Rhodiola chemical components was built;(2)A recovery test was performed on10target proteins with root-mean-square deviation(RMSD)as the evaluation criterion,the docking parameter was identified and target database was built;(3)Molecular docking between187chemicalcomponents and10targets,and as well as their parameters were run through the databases.The top5%chemical components were regardedas positive to establish the compound-target interaction network graph.Results18compounds in Rhodiola interacted with more than3targets,which proved the muti-target molecular mechanism of Rhodiola.Conclusions Some active constituents previously reported had beenscreened out,such as Rhodionin,Rhodiosin,Crenulatin,Pharienside and Pyridrde.The structure and target information was listed to providereference for the determination of targets and future research and development on pharmaceutical components of Rhodiola.

关 键 词：红景天 高原反应 靶标 HIF-1Α 分子对接 

分 类 号：O64[理学—物理化学]