摘要
目的:基于网络药理学预测二至丸治疗良性前列腺增生的作用靶点,探讨其多成分-多靶点-多通路的作用机制,对其治疗良性前列腺增生的分子机制进行科学阐释。方法:采用网络药理学软件生物反应路径分析(IPA)构建"化合物-靶点-疾病"的网络;对二至丸作用靶点构建蛋白互作网络(PPI),进行基因富集分析(GO)功能注释和京都基因和基因组百科全书(KEGG)通路富集分析,预测二至丸治疗前列腺增生的作用机制。结果:二至丸总共有19个化合物在IPA中,并且芹菜素(Apigenin),木犀草素(Luteolin),熊果酸(Oleanolic acid)和槲皮苷(Quercitrin) 4个化合物是女贞子和墨旱莲共有化合物,是二至丸的主要物质基础;毒蕈碱型乙酰胆碱受体M3(CHRM3),毒蕈碱型乙酰胆碱受体M2(CHRM2),尿激酶型纤溶酶原激活物受体(PLAUR),激肽释放酶3(KLK3),钙黏蛋白1(CDH1),趋化因子3(CCL3)和金属蛋白酶1(MMP1)等二至丸治疗前列腺增生的关键靶点; PPI网络靶点蛋白有20条GO功能富集和5条主要的KEGG通路富集,并对相关靶点进行Docking验证。结论:二至丸通过激活MMP1和抑制KLK3以及CCL3蛋白表达,诱导细胞凋亡和抑制细胞增殖,干预丝裂原活化蛋白激酶/胞外信号调节激酶(MAPK/ERK),核转录因子-κB(NF-κB)等信号通路发挥抑制前列腺增生的作用。
Objective: To explain the 'multi-components,multi-targets,multi-pathways'mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network,then the classified enrichment analysis of gene ontology(GO) and pathway enrichment analysis(KEGG) were carried out on the main function of its gene sets,so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result:Erzhiwan has 19 components in IPA;and apigenin, luteolin, oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3(CHRM3),muscarinic acetylcholine receptor M2(CHRM2),urokinase plasminogen activator receptor(PLAUR),kinin releasing enzyme 3(KLK3),cadherin 1(CDH1),chemokines 3(CCL3)and metalloproteinase-1(MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways,and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions,inducing apoptosis,inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).
作者
陶蕊
樊官伟
毛浩萍
王小莹
苗琳
高秀梅
TAO Rui;FAN Guan-wei;MAO Hao-ping;WANG Xiao-ying;MIAO Lin;GAO Xiu-mei(Tianjin University of Traditional Chinese Medicine(TCM),Tianjin State Key Laboratory of Modern Chinese Medicine,Tianjin Key Laboratory of TCM Pharmacology,Tianjin 300193,China;The First Affiliated Hospital of Tianjin University of TCM,Tianjin 300193,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第5期208-213,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81630106)
关键词
网络药理学
二至丸
女贞子
墨旱莲
良性前列腺增生
network pharmacology
Erzhiwan
Ligustri Lucidi Fructus
Echiptae Herba
benign prostatic hyperplasia
