利用液相和质谱联用技术以及网络药理学分析藏药五味甘露药浴汤散治疗痛风关节炎的有效成分及作用机制  

Analysis of the effective components and possible mechanism of tibetan medicine Wuwei Ganlu yaoyu decoction powder in treating gouty arthritis by liquid chromatography mass spectrometry and network pharmacology

作　　者：丁银 张琨 苟晓玲 彭家艳 罗玉婷 曾宇骄 王天虹[1] 范刚[1,2] DING Yin;ZHANG Kun;GOU Xiao-ling;PENG Jia-yan;LUO Yu-ting;ZENG Yu-jiao;WANG Tian-hong;FAN Gang(College of Ethnic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学民族医药学院,成都611137 [2]成都中医药大学药学院,成都611137

出　　处：《中国新药杂志》2023年第17期1783-1794,共12页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81803846);国家重点研发计划资助项目(2019YFC1712302)。

摘　　要：目的:探究五味甘露药浴汤散治疗痛风关节炎(GA)的有效成分和潜在机制。方法:利用超高效液相色谱⁃四极杆⁃静电场轨道阱高分辨质谱(UPLC⁃Q⁃Exactive⁃Orbitrap⁃MS)鉴定五味甘露药浴汤散的主要化学成分,通过Swiss Target数据库筛选成分靶点,运用GeneCards,OMIM等数据库筛选疾病靶点,采用STRING平台构建PPI网络选取关键靶点,利用DAVID数据库对药物和疾病共有靶点进行GO和KEGG通路富集,讨论五味甘露药浴汤散治疗GA的作用机制。此外,通过Cytoscape 3.9.1软件构建“药物⁃成分⁃靶点⁃疾病”网络,并利用Maestro软件对成分与核心靶点进行分子对接,筛选出有效成分。结果:共鉴定出52个化合物,包括24个黄酮类成分、5个生物碱类成分、10个有机酸类成分、5个酚类成分、5个苯丙素类成分、2个萜类成分以及1个烷烃类成分。网络药理学分析发现五味甘露药浴汤散成分靶点520个,交集靶点141个,筛选出5个核心靶点(SRC,STAT3,PIK3CA,MAPK1,HSP90AA1)。分子对接结果显示木犀草苷等6个成分与5个核心靶点具有较好的结合能力。结论:五味甘露药浴汤散治疗GA的活性成分为木犀草苷、海波拉亭⁃7⁃O⁃β⁃D⁃吡喃葡萄糖苷、海波拉亭⁃7⁃O⁃β⁃D⁃吡喃木糖苷、槲皮素、柚皮素和木犀草素,其机制可能与这些成分作用于SRC,STAT3,PIK3CA等靶点调控PI3K⁃Akt,Ras,MAPK等信号通路有关。Objective:The present study explored the active ingredients and potential mechanism of Wuwei Ganlu yaoyu decoction powder in the treatment of gouty arthritis(GA).Methods:The main chemical components of Wuwei Ganlu yaoyu decoction powder were identified by UPLC⁃Q⁃Exactive⁃Orbitrap⁃MS.The target compounds were screened from the identified compounds by Swiss Target database.The databases genecards,OMIM and others were used to screen disease targets,STRING to build PPI network and select key targets,DAVID to enrich GO and KEGG pathways of common targets of drug diseases.Based on these,we discussed the mechanism of Wuwei Ganlu yaoyu decoction powder in the treatment of GA.In addition,the“drug⁃component⁃target⁃disease”network was constructed by using Cytoscape 3.9.1 software,and Maestro software was used to conduct molecular docking between components and core targets to screen effective components.Results:A total of 52 compounds were identified,including 24 flavonoids,5 alkaloids,10 organic acids,5 phenols,5 phenylpropanoids,2 terpenoids and 1 alkane.According to the analysis of network pharmacology,there were 520 component targets and 141 intersection targets of Wuwei Ganlu yaoyu decoction powder,and 5 core targets were screened(SRC,STST3,PIK3CA,MAPK1,HSP90AA1).Molecular docking showed that six components such as Luteolin had good binding ability with five core targets.Conclusion:The active components of Wuwei Ganlu yaoyu decoction powder in the treatment of GA are luteolin,hyperoxin⁃7⁃O⁃β⁃D⁃glucopyranoside,Hyprolatine⁃7⁃O⁃β⁃D⁃xylopyranoside,quercetin,naringin and luteolin,which may be related to the action on targets like SRC,STAT3,PIK3CA and others to regulate the signal pathways of PI3K Akt,Ras,MAPK,etc.

关 键 词：五味甘露药浴汤散 痛风关节炎 超高效液相色谱⁃四极杆⁃静电场轨道阱高分辨质谱 网络药理学 分子对接 

分 类 号：R965[医药卫生—药理学]