摘要
利用网络药理学和实验验证揭示壮骨镇痛胶囊治疗骨转移癌痛的活性成分及作用机制。首先,运用中药系统药理学数据库平台(TCMSP)和中药分子机制的生物信息学分析工具(BATMAN-TCM)获取壮骨镇痛胶囊的化学成分及靶点,GeneCards数据库获得骨转移癌痛的疾病靶点,然后通过Venn、Cytoscape、String及DAVID数据库分析壮骨镇痛胶囊治疗骨转移癌痛的潜在活性成分、核心靶点及作用通路之间的关系,使用Auto Dock进行分子对接分析,最后通过建立骨转移癌痛大鼠模型进行实验验证。网络药理学结果显示壮骨镇痛胶囊治疗骨转移癌痛的活性成分可能为槲皮素、木犀草素、异补骨脂素,关键靶点可能为蛋白激酶B(protein kinase B,AKT1)、肿瘤蛋白53(tumor protein 53,TP53)、表皮生长因子受体(epidermal growth factor receptor,EGFR)等,主要富集于丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、磷脂酰肌醇激酶(phosphatidylinositol 3 kinase,PI3K)-AKT、核因子κB受体(nuclear factor kappa B,NF-κB)等通路。实验结果表明壮骨镇痛胶囊及其活性成分能有效改善骨转移癌痛大鼠的疼痛行为学和骨质破坏,降低PI3K、p-AKT1/AKT1、p-P38/P38、磷酸化-胞外信号调节激酶1/2(phosphorylation-extracellular signal regulated kinase,p-ERK1/2)/ERK1/2、p-c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)/JNK、p-P65/P65及p-人核因子κB抑制蛋白α(inhibitor of nuclear factor-κBα,p-IKBα)/IKBα的蛋白表达水平(P<0.05)。因此,壮骨镇痛胶囊及其活性成分槲皮素、木犀草素和异补骨脂素能有效改善骨转移癌痛,其作用机制可能与抑制MAPK、PI3K-AKT及NF-κB通路有关。
This study aims to reveal the active ingredients and mechanism of action of Zhuanggu Zhentong capsule in the treatment of cancer-induced bone pain by using network pharmacology and experimental verification.Firstly,the Traditional Chinese Medicine Systems Pharmacology Platform(TCMSP)and the bioinformatics analysis tool for molecular mechanics of traditional Chinese medicine(BATMAN-TCM)were used to obtain the chemical composition and targets of the Zhuanggu Zhentong capsule.The GeneCards database was used to obtain the disease targets of cancer-induced bone pain.Then,the relationship between the potential active ingredients,core targets,and action pathways of Zhuanggu Zhentong capsule in treating cancer-induced bone pain were analyzed using Venn,Cytoscape,String,and DAVID databases.Perform molecular docking analysis using Auto Dock,and finally validate the experimental results by establishing a rat model of cancer-induced bone pain.The results of network pharmacology show that the active ingredients of Zhuanggu Zhentong capsule for treating cancer-induced bone pain may be quercetin,luteolin,and angelicin,and the key targets may be protein kinase B(AKT1),tumor protein 53(TP53),epidermal growth factor receptor(EGFR),which mainly enriched in mitogen-activated protein kinase(MAPK),phosphatidylinositol 3 kinase(PI3K)-AKT,nuclear factor kappa B receptor(NF-κB)and other pathways.The in vivo experimental results showed that Zhuanggu Zhentong capsule and their active ingredients can effectively improve the pain behavior and bone destruction of rats with cancer-induced bone pain,reduce the protein expression levels of PI3K,p-AKT1/AKT1,p-P38/P38,phosphorylation extracellular signal regulated kinase 1/2(p-ERK1/2)/ERK1/2,p-c-Jun N-terminal kinase(JNK)/JNK,p-P65/P65,and p-inhibitor of nuclear factor kappa Bα(p-IKBα)/IKBα(P<0.05).Therefore,Zhuanggu Zhentong capsule and their active ingredients quercetin,luteolin,and angelicin can effectively improve the pain of cancer-induced bone pain,and their mechanism of action may be re
作者
赖桂花
曹建雄
周君
王菲
聂多锐
文玲
马漪
LAI Gui-hua;CAO Jian-xiong;ZHOU Jun;WANG Fei;NIE Duo-rui;WEN Ling;MA Yi(The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410007,China;Hunan University of Traditional Chinese Medicine,Changsha 410208,China;Rehabilitation Medicine Center,the First Affiliated Hospital,Hengyang Medical School,University of South China;Department of Rehabilitation,the First Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China)
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2024年第12期2145-2158,共14页
Natural Product Research and Development
基金
湖南省重点研发计划(2018SK2127)
湖南省自然科学基金青年项目(2023JJ40595)
南华大学临床医学4310项目
中国博士后科学基金第75批面上项目(1353)。
关键词
壮骨镇痛胶囊
骨转移癌痛
网络药理学
分子对接
作用机制
Zhuanggu Zhentong capsule
cancer-induced bone pain
network pharmacology
molecular docking
mechanism of action
