基于网络药理学的软紫草“凉血”在热射病防护上的药效学研究  

Network Pharmacology Study of Arnebia euchroma in the Protective Effect of Heat Stroke

作　　者：章亮 罗琼 何欢欢 刘江伟[2] 唐赟 张波 ZHANG Liang;LUO Qiong;HE Huan-huan;LIU Jiang-wei;TANG Yun;ZHANG Bo(Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,Ministry of Education,School of Pharmacy,Shihezi University,Shihezi 832000,China;The Key Labortary of the Special Environmental Medicine of Xinjiang,General Hospital of Xinjiang Military Region,Urumqi 830000,China;Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200082,China)

机构地区：[1]石河子大学药学院,新疆植物药资源利用教育部重点实验室,新疆石河子832000 [2]新疆军区总医院,新疆特殊环境医学重点实验室,乌鲁木齐830000 [3]华东理工大学药学院,上海市新药设计重点实验室,上海200082

出　　处：《中国药学杂志》2020年第17期1425-1432,共8页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(U1603122);兵团科技创新领域中青年领军人才项目资助(2018CB019);新疆生产建设兵团英才项目资助(第二批)。

摘　　要：目的运用网络药理学方法预测软紫草凉血功效的物质基础,探讨软紫草可能的热射病防护作用,并加以验证。方法基于数据库和文献检索收集软紫草的化学成分,利用admet SAR方法筛选潜在活性成分,bSDTNBI方法预测潜在活性成分作用靶标,从OMIM数据库中检索热射病相关靶标,运用STRING数据库构建“预测靶标-疾病靶标”蛋白互作网络,分析筛选关键作用靶标。建立热应激诱导小鼠热射病模型,对关键活性成分(紫草素)的热射病防护作用进行药效学验证。结果共收集软紫草化学成分165个,筛选出26个潜在活性成分,作用于93个靶标,网络分析确定其“凉血”功效的物质基础主要是萘醌类化合物。“预测靶标-疾病靶标”蛋白互作网络中软紫草与热射病共享多个靶标,提示软紫草可能具有热射病防护作用,46个关键靶标主要参与炎症反应、神经递质传导、氧化还原和凝血等生物学过程和相关通路。紫草素可以显著延长热射病小鼠生存时间,减轻急性反应,改善组织脏器损伤。结论软紫草可能通过抑制炎症反应、促进血液循环、保护中枢神经,从而改善多器官损伤,发挥热射病防护作用。OBJECTIVE To predict the material basis of the“cooling blood”effect of Arnebia euchroma,and discusses its potential pathway and mechanism via network pharmacology.METHODS The chemical constituents of Arnebia euchroma were collected based on database and literature search,the potential active components were filtered by admet SAR method,the targets of potential active ingredients were predicted by bSDTNBI method,the heat stroke related targets was retrieved from OMIM database.The STRING database was used to construct a"predicted target-disease target"protein interaction network,analyze and filter the key targets.A heat stroke model by heat stress-induced in mice to verify the efficacy of the key active ingredient(shikonin)for heat stroke protection was established.RESULTS A total of 165 chemical constituents of Arnebia euchroma were filtered and 26 potential active ingredients were filtered out to act on 93 targets.Network analysis confirmed that naphthoquinone compounds were the main material basis of its"cooling blood"effect.Arnebia euchroma and heat stroke share multiple targets in the"predicted target-disease target"protein interaction network,suggesting that Arnebia euchroma may have protective effects on against heat stroke(HS).Forty-six key targets were mainly involved in biological processes and pathways such as inflammation,neurotransmitter conduction,redox and coagulation.Pharmacodynamic studies showed that shikonin could significantly prolong the survival time of mice with HS,reduce acute reactions and improve tissue organ damage.CONCLUSION In summary,Arnebia euchroma may inhibit the inflammatory responses,promote blood circulation,protect the central nervous system,thereby improving multiple organ damage,and play a protective role in against HS.

关 键 词：热射病 软紫草 凉血 紫草素 网络药理学 

分 类 号：R965[医药卫生—药理学]