基于网络药理学探究二至丸抑制良性前列腺增生的分子机制

陶蕊; 樊官伟; 毛浩萍; 王小莹; 苗琳; 高秀梅

doi:10.13422/j.cnki.syfjx.20190508

您当前的位置：

首页 >

文章列表页 >

基于网络药理学探究二至丸抑制良性前列腺增生的分子机制

数据挖掘 | 更新时间：2021-02-09

- 基于网络药理学探究二至丸抑制良性前列腺增生的分子机制
- Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology
- 中国实验方剂学杂志 2019年25卷第5期页码：208-213
- 作者机构：
  
  1.天津中医药大学　中医药研究院，天津市现代中药重点实验室，天津市中药药理学重点实验室，天津　 300193；
  2.天津中医药大学　第一附属医院，天津　 300193
- 作者简介：
  
  陶蕊，在读博士，从事中药药理研究，E-mail: taorui2013tjutcm@126.com
  苗琳，博士，副研究员，从事中药药理研究，Tel: 022-59596171，E-mail: mmmlin7180@hotmail.com
- 基金信息：
  
  国家自然科学基金项目(81630106)
- DOI：10.13422/j.cnki.syfjx.20190508
  中图分类号： R2-0;R22;R285.5;R289
- 收稿日期：2018-08-31，
  
  网络出版日期：2018-11-21，
  
  纸质出版日期：2019-03-05
- 稿件说明：
移动端阅览
陶蕊, 樊官伟, 毛浩萍, 等. 基于网络药理学探究二至丸抑制良性前列腺增生的分子机制[J]. 中国实验方剂学杂志, 2019,25(5):208-213.

Rui TAO, Guan-wei FAN, Hao-ping MAO, et al. Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 208-213.
陶蕊, 樊官伟, 毛浩萍, 等. 基于网络药理学探究二至丸抑制良性前列腺增生的分子机制[J]. 中国实验方剂学杂志, 2019,25(5):208-213. DOI： 10.13422/j.cnki.syfjx.20190508.

Rui TAO, Guan-wei FAN, Hao-ping MAO, et al. Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 208-213. DOI： 10.13422/j.cnki.syfjx.20190508.

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-

B(NF-

B)等信号通路发挥抑制前列腺增生的作用。

Abstract

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)-

B(NF-

B).

关键词

Keywords

references

FU Y , HAN S , WANG L , et al . Comparison of characteristics of benign prostatic hyperplasia (bph) patients treated with finasteride and alpha blocker combination therapy versus alpha blocker monotherapy in china: an analysis of electronic medical record data [J]. Adv Ther , 2018 , 35 ( 8 ): 1191 - 1198 .

Salem R , Hairston J , Hohlastos E , et al . Prostate artery embolization for lower urinary tract symptoms secondary to benign prostatic hyperplasia: results from a prospective fda-approved investigational device exemption study [J]. Urology , 2018 , 120 : 205 - 210 .

ZHANG J , LI X , YANG B , et al . Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis [J]. World J Urol , 2018 , doi: 10.1007/s00345-018-2370-2 doi:10.1007/s00345-018-2370-2 .

Mallikarjuna C , Nayak P , Ghouse S M , et al . Transurethral enucleation with bipolar energy for surgical management of benign prostatic hyperplasia: our initial experience [J]. Indian J Urol , 2018 , 34 ( 3 ): 219 - 222 .

张永宁，袁丽超，佟书娟，等．二至丸、地黄煎影响小鼠免疫功能的比较研究 [J]. 中国实验方剂学杂志， 2012 , 18 ( 8 ): 159 - 162 .

尚广彬，曾莉萍，赵益，等．二至丸对诱发性乳腺癌组织中VEGF和MMP9表达的影响 [J]. 中国实验方剂学杂志， 2013 , 19 ( 13 ): 270 - 273 .

闫冰，蔡秀江，姚卫峰，等．二至丸保肝活性成分群对CCl4致小鼠急性肝损伤保护作用研究 [J]. 中国中药杂志， 2012 , 37 ( 9 ): 1303 - 1306 .

闫冰，丁安伟，张丽．二至丸提取物对小鼠四氯化碳急性肝损伤的保护作用 [J]. 中国中药杂志， 2010 , 35 ( 22 ): 3080 - 3083 .

赵海梅，周步高，王馨，等．二至丸预防和治疗性给药对大鼠损伤后肝细胞再生障碍的保护作用 [J]. 中国实验方剂学杂志， 2017 , 23 ( 16 ): 128 - 132 .

Calogero A E , Burgio G , Condorelli R A , et al . Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction [J]. Aging Male , 2018 , 2018 ( 3 ): 1 - 8 .

YU F , SHEN X Y , FAN L , et al . Genome-wide analysis of genetic variations assisted by ingenuity pathway analysis to comprehensively investigate potential genetic targets associated with the progression of hepatocellular carcinoma [J]. Eur Rev Med Pharmacol Sci , 2014 , 18 ( 15 ): 2102 - 2108 .

Lein M , Nowak L , Jung K , et al . Metalloproteinases (MMP-1, MMP-3) and their inhibitors (TIMP) in blood plasma of patients with prostate carcinoma [J]. Urologe A , 1998 , 37 ( 4 ): 377 - 381 .

Soni A , Bansal A , Mishra A K , et al . Association of androgen receptor, prostate-specific antigen, and CYP19gene polymorphisms with prostate carcinoma and benign prostatic hyperplasia in a north Indian population [J]. Genet Test Mol Biomarkers , 2012 , 16 ( 8 ): 835 - 840 .

WANG X , LIN W J , Izumi K , et al . Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation [J]. J Biol Chem , 2012 , 287 ( 22 ): 18376 - 18385 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基于网络药理学探讨二至丸治疗肝细胞癌的作用机制

基于网络药理学的女贞子-黄芪药对的抗癌机制

基于5种特征性成分综合评价二至丸的质量

二至丸抗肝纤维化活性成分-靶点-通路的网络预测

基于Nrf2通路与巨噬细胞活化探讨克癃胶囊治疗良性前列腺增生的作用机制