基于体内药效学结合网络药理学的丝穗金粟兰抗炎镇痛作用研究  

Anti-inflammatory and Analgesic Mechanism of Chloranthus fortunei Based on in vivo Pharmacodynamics Combined with Network Pharmacology

作　　者：卢显兴 奉建芳 丘琴[1,2] 黄秋艳 陈玉敏 LU Xian-xing;FENG Jian-fang;QIU Qin;HUANG Qiu-yan;CHEN Yu-min(Guangxi University of Chinese Medicine,Nanning 530200,China;Guangxi Superior Chinese Patent Medicine and National Medicine Development Engineering Technology Center,Nanning 530200,China)

机构地区：[1]广西中医药大学,广西南宁530200 [2]广西优势中成药与民族药开发工程技术研究中心,广西南宁530200

出　　处：《中国现代中药》2022年第7期1253-1261,共9页Modern Chinese Medicine

基　　金：国家重点研发计划项目(2019YFC1712300);中药学广西一流学科项目(桂教科研〔2018〕12号);广西科技基地和人才专项(桂科AD20238058)。

摘　　要：目的:采用体内药效学实验结合网络药理学方法探究丝穗金粟兰的抗炎镇痛机制。方法:通过二甲苯致小鼠耳肿胀、角叉菜胶致小鼠足肿胀、乙酸致小鼠扭体实验评价丝穗金粟兰抗炎镇痛作用;经文献查阅并结合PubChem、SwissADME、SwissTargetPrediction数据库对丝穗金粟兰已知成分及其对应靶点进行搜集,经GeneCards数据库搜索得到的炎症和疼痛相关靶点进行交互分析得到共同靶点。通过蛋白质-蛋白质相互作用(PPI)分析、基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,构建丝穗金粟兰成分-靶点-疾病网络,探讨丝穗金粟兰抗炎镇痛的作用机制,选取关键潜在靶点及活性化合物,运用AutoDock软件进行分子对接。结果:与模型组比较,丝穗金粟兰水提物高剂量可以明显缓解3个造模剂所致小鼠炎症和疼痛(P<0.05)。网络预测分析共收集到31个活性成分、40个关键靶点、62条通路与丝穗金粟兰抗炎镇痛相关,分子对接结果显示潜在药效物质与关键靶点前列腺素G/H合酶2(PTGS2)、基质金属蛋白酶9(MMP9)、丝裂原活化蛋白激酶1(MAPK1)、信号传导与转录激活因子3(STAT3)和白蛋白(ALB)结合活性良好。结论:丝穗金粟兰具有一定抗炎镇痛作用,其可能通过β-榄香醇、莽草酸、银线草醇E、银线草醇I等化合物调控PTGS2、MMP9、MAPK1、STAT3和ALB等靶点,从而抑制肿瘤坏死因子(TNF)、核转录因子-κB(NF-κB)、磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(Akt)等通路来发挥抗炎镇痛的作用。Objective:To decipher the anti-inflammatory and analgesic mechanism of Chloranthus fortunei(A.Gray)Solms-Laub based on in vivo pharmacodynamics combined with network pharmacology.Methods:The anti-inflammatory and analgesic effects of C.fortunei were evaluated with the mouse models of ear swelling induced by xylene,footpad swelling induced by carrageenin,and writhing induced by acetic acid.The known components and their corresponding targets of C.fortunei were obtained via literature review as well as PubChem,SwissADME,and SwissTargetPrediction.The targets associated with inflammation and pain were obtained from GeneCards.The common targets shared by the herb and inflammation/pain were then identified.Through protein-protein interaction(PPI)network,gene ontology(GO)annotation,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,the"component-target-disease"network was constructed to reveal the anti-inflammatory and analgesic mechanism of C.fortunei.The key potential targets and active compounds were selected for molecular docking in AutoDock.Results:The high-dose extract of C.fortunei alleviated the inflammation and pain caused by the three modeling agents in mice(P<0.05).A total of 40 active components and 31 key targets were predicted to be associated the anti-inflammatory and analgesic effects,and the targets were mainly enriched in 62 KEGG pathways.The molecular docking results showed that predicted active components had good binding activity with the key targets prostaglandin endoperoxide synthase 2(PTGS2),matrix metallopeptidase 9(MMP9),mitogen-activated protein kinase 1(MAPK1),signal transducer and activator of transcription 3(STAT3),and albumin(ALB).Conclusion:C.fortunei has anti-inflammatory and analgesic effects.The active componentsβ-elemol,shikimic acid,shizukaol E,and shizukaol I in this herb regulate PTGS2,MMP9,MAPK1,STAT3,and ALB to inhibit tumor necrosis factor(TNF),nuclear factor kappa-B(NF-κB),and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)pathways,thus exerting the

关 键 词：丝穗金粟兰 抗炎 镇痛 网络药理学 作用机制 

分 类 号：R285[医药卫生—中药学]