基于网络药理学和实验验证的蒙药如达-6治疗胃溃疡作用机制研究  

Study on the Action Mechanism of Mongolian Medicine Ruda-6 in Treating Gastric Ulcer Based on Network Pharmacology and Experimental Verification

作　　者：风兰 包特日格乐 付明海[1] 拉喜那木吉拉 李国瑞[2] 陈永胜 Fenglan;BAO Terigele;FU Ming-hai;Laxinamujila;LI Guo-rui;CHEN Yong-sheng(College of Mongolian Medicine and Pharmacy,Inner Mongolia Minzu University,Tongliao 028043,China;College of Life Science and Food Engineering,Inner Mongolia Minzu University,Tongliao 028043,China;Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences,Changchun 130000,China)

机构地区：[1]内蒙古民族大学蒙医药学院,内蒙古通辽028043 [2]内蒙古民族大学生命科学与食品学院,内蒙古通辽028043 [3]中国科学院长春光学精密机械与物理研究所,吉林长春130000

出　　处：《内蒙古民族大学学报（自然科学版）》2023年第3期257-268,共12页Journal of Inner Mongolia Minzu University：Natural Sciences

基　　金：应用光学国家重点实验室开放基金项目(SKLA02020001A19);内蒙古自治区高等学校青年科技人才发展项目(NJYT22048);中央引导地方科技发展项目(N2021ZY0015)。

摘　　要：目的:通过网络药理学和动物实验,探讨蒙药如达-6治疗胃溃疡的潜在活性成分、核心靶点和作用机制。方法:利用TCMSP、SwissTargetPredition、BATMAN-TCM、GeneCards、OMIM、PharmGkb、TTD和Drugbank数据库预测和筛选如达-6潜在活性成分及其治疗胃溃疡靶点。利用STRING数据库进行蛋白-蛋白(Protein-protein interaction,PPI)互作分析,使用Metascape数据库进行GO功能注释和KEGG通路富集分析。通过Cytoscape3.8.0软件绘制PPI网络和“成分-靶点”网络。建立吲哚美辛诱导的胃溃疡大鼠模型,观察如达-6对胃溃疡大鼠的胃保护作用,再利用q RT-PCR方法检测关键靶点的mRNA表达水平。结果:共筛选出如达-6的58个潜在活性成分和137个治疗胃溃疡靶点。通过PPI网络分析得到STAT3、PIK3CA、SRC、RELA、TP53、MAPK1、AKT1、JUN、CTNNB1和PTPN11等10个核心靶点;通过“成分-靶点”网络分析得到槲皮素、木犀草素、山柰酚、β-谷甾醇、豆甾醇、异鼠李素、华良姜素、5-羟基-7-甲氧基-2-(3,4,5-三甲氧基-苯基)色酮、3-甲基樟脑酚以及N-(2,5-二甲氧基苯基)-4-甲氧基苯甲酰胺等10个关键成分。功能富集分析显示,如达-6可能通过癌症的途径、人巨细胞病毒感染、PI3K/Akt信号通路、癌症中的蛋白聚糖、脂质与动脉粥样硬化以及MAPK等信号通路发挥抗胃溃疡作用。实验验证结果表明,如达-6对吲哚美辛诱导的胃溃疡大鼠具有预防性保护作用,可缓解胃组织病理学改变,并增加胃组织PIK3CA、TP53、MAPK1和AKT1的mRNA表达水平(P<0.05)。结论:通过网络药理学分析和实验验证,初步揭示了蒙药如达-6通过多成分、多靶点发挥抗胃溃疡作用。Objective:To explore the potential active components,hub targets and action mechanism of Mongolian medicine Ruda-6(RD-6)in the treatment of gastric ulcer(GU)through network pharmacology and animal ex⁃periments.Methods:The potential active components and therapeutic targets of Ruda-6 against gastric ulcer were predicted and screened through TCMSP,SwissTargetPredition,BATMAN-TCM,GeneCards,OMIM,Pharma⁃Gkb,TTD,and Drugbank databases.Protein-protein interaction(PPI)analysis was performed through the STRING database,and GO functional annotation and KEGG pathway enrichment analysis were performed by Metascape database.The PPI network and“component-target”network were mapped by Cytoscape3.8.0 soft⁃ware.Then,the gastric ulcer rat model was established by indomethacin-induction,and the gastric protective ef⁃fect of Ruda-6 on gastric ulcer rats was observed.In addition,the mRNA expression level of key targets was de⁃tected by qRT-PCR.Results:A total of 58 potential active ingredients and 137 anti-gastric ulcer targets of Ru⁃da 6 were screened.PPI analysis revealed 10 hub targets including STAT3,PIK3CA,SRC,RELA,TP53,MAPK1,AKT1,JUN,CTNNB1,and PTPN11.The“component-target”network analysis indicated 10 core compo⁃nents including quercetin,luteolin,kaempferol,β-sitosterol,stigmasterol,isorhamnetin,kumatakenin,5-hydroxy 7-methoxy-2-(3,4,5-trimethoxy-phenyl)chromone,3-Methyl camphor phenol,and N-(2,5-dimethoxyphe⁃nyl)-4-methoxybenzamide.Functional analysis showed that Ruda-6 may play an anti-gastric ulcer role through pathways in cancer,human cytomegalovirus infection,PI3K/Akt signaling pathway,proteoglycans in cancer,lipids and atherosclerosis,MAPK signaling pathway,etc.The experimental verification results showed that Ruda-6 had a preventive protective effect on indomethacin-induced gastric ulcer in rats,alleviated gastric histopathology inju⁃ry,and increased the mRNA expression levels of PIK3CA,TP53,MAPK1 and AKT1 in gastric tissue(P<0.05).Conclusion:The network pharmacological analysis and experimenta

关 键 词：蒙药 如达-6 胃溃疡 网络药理 实验验证 

分 类 号：R961[医药卫生—药理学]