Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology

Jiacheng LIN; Xuanlu ZHENG; Chenghui WANG; Weidong PAN

doi:10.16306/j.1008-861x.2022.S1.040

您当前的位置：

首页 >

文章列表页 >

Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology

Experiment Research | 更新时间：2022-08-29

- Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue S1, Pages: 180-186(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院中心实验室（上海　201203）
  2.上海中医药大学附属曙光医院脑病科（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.S1.040
  CLC：
扫描看全文
林佳成,郑煊璐,王呈蕙等.基于网络药理学原理探讨健脾补肾方治疗肌萎缩侧索硬化症的机制[J].上海中医药大学学报,2022,36(S1):180-186.

LIN Jiacheng,ZHENG Xuanlu,WANG Chenghui,et al.Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):180-186.
林佳成,郑煊璐,王呈蕙等.基于网络药理学原理探讨健脾补肾方治疗肌萎缩侧索硬化症的机制[J].上海中医药大学学报,2022,36(S1):180-186. DOI： 10.16306/j.1008-861x.2022.S1.040.

LIN Jiacheng,ZHENG Xuanlu,WANG Chenghui,et al.Exploring mechanism of Jianpi Bushen Decoction on amyotrophic lateral sclerosis based on network pharmacology[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):180-186. DOI： 10.16306/j.1008-861x.2022.S1.040.

摘要

目的,2,本研究通过网络药理学的研究方法，从分子机制和物质基础的角度探讨健脾补肾方的作用机制。,方法,2,利用疾病数据库与中药数据库获取健脾补肾方治疗肌萎缩侧索硬化症（ALS）的潜在靶点，利用DAVID数据库进行京都基因与基因组百科全书（KEGG）通路和基因本体（GO）富集分析，利用String数据库建立蛋白-蛋白互相作用（PPI）网络，利用Cytoscape软件建立和分析靶点网络。,结果,2,KEGG富集结果提示健脾补肾方治疗ALS的机制可能涉及对细胞存活（磷脂酰肌醇3-激酶/蛋白激酶B通路，PI3K/Akt通路）、炎症（丝裂原活化蛋白激酶通路，MAPKs通路）、钙离子信号通路的调控。GO分析结果提示健脾补肾方主要调控细胞凋亡、蛋白磷酸化、蛋白结合等过程。PPI网络提示其主要调控的蛋白家族为谷氨酸离子型受体家族、MAPKs、半胱氨酸蛋白酶家族。靶点网络分析提示其调控的主要靶点为细胞凋亡相关基因，包括半胱氨酸蛋白酶3（,CASP3,）、胱抑素C（,CYCS,）、肿瘤蛋白53（,TP53,）。健脾补肾方的主要有效成分可能是槲皮素、木犀草素、山柰酚等。,结论,2,健脾补肾方可能通过多途径抑制神经元死亡和神经炎症治疗ALS。

Abstract

Objective： This study aims to explore the molecular mechanism and material basis of Jianpi Bushen Decoction via network pharmacology.,Methods,2,Potential targets of Jianpi Bushen Decoction on amyotrophic lateral sclerosis （ALS） were obtained by disease database and traditional Chinese medicine database. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） enrichment analysis were performed using DAVID database. The protein-protein interaction （PPI） network was constructed using String database. And target network was analyzed and established by Cytoscape software.,Results,2,KEGG enrichment analysis showed that the mechanism of Jianpi Bushen Decoction on ALS may involve the cell survival （phosphatidylinositol 3-kinase/protein kinase B pathway， PI3K/Akt pathway）， inflammation （mitogen-activated protein kinase pathway， MAPKs signaling）， and calcium signaling pathway. GO enrichment analysis showed that Jianpi Bushen Decoction could regulate apoptosis， protein phosphorylation， protein binding and other processes. PPI network showed that glutamate ionic receptor family， MAPKs， and cysteine aspirate protease family were the main protein family. Target network analysis suggested that the main regulatory targets were apoptosis related genes， including cysteine protease 3 （,CASP3,）， cystatin C （,CYCS,） and tumor protein 53 （,TP53,）. Quercetin， luteolin， and kaempferol may be the potential active ingredients of Jianpi Bushen Decoction.,Conclusion,2,Jianpi Bushen Decoction may treat ALS by inhibiting neuronal death and neuroinflammation through multiple pathways.

关键词

健脾补肾方肌萎缩侧索硬化症网络药理学谷氨酸受体

Keywords

Jianpi Bushen Decoctionamyotrophic lateral sclerosisnetwork pharmacologyglutamate receptors

references

GUO W T， VANDOORNE T， STEYAERT J， et al. The multifaceted role of kinases in amyotrophic lateral sclerosis：genetic，pathological and therapeutic implications［J］. Brain， 2020， 143： 1651-1673.

KIERNAN M C， VUCIC S， CHEAH B C， et al. Amyotrophic lateral sclerosis［J］. Lancet， 2011， 377： 942-955.

OBRADOR E， SALVADOR-PALMER R， LÓPEZ-BLANCH R， et al. The link between oxidative stress，redox status，bioenergetics and mitochondria in the pathophysiology of ALS［J］. Int J Mol Sci， 2021， 22（12）： 6352.

BADING H. Therapeutic targeting of the pathological triad of extrasynaptic NMDA receptor signaling in neurodegenerations［J］. J Exp Med， 2017， 214： 569-578.

廖伟龙，姜文斐，高鹏琳，等. 基于中医基础理论从脾论治肌萎缩侧索硬化症［J］. 中西医结合心脑血管病杂志，2019， 17（7）： 1029-1031.

PAN W D， SU X J，BAO J， et al. Open randomized clinical trial on JWSJZ decoction for the treatment of ALS Patients［J］. Evid Based Complement Alternat Med，2013， 2013： 347525.

暴洁，符茂东，沈冰洁，等.加味四君子汤治疗肌萎缩侧索硬化的临床研究［J］.医药导报，2016， 35（S1）： 43-45.

潘卫东，SHIN K，吴春岚，等. 加味四君子汤对肌萎缩侧索硬化症AR2小鼠运动功能的影响［J］. 上海中医药大学学报，2013， 27（1）： 60-63.

朱玮，王明哲，李婷婷，等. 健脾补肾方治疗肌萎缩侧索硬化的机制研究［J］. 神经病学与神经康复学杂志，2021， 17（2）： 57-62.

马腾，黄银兰，李玲. 中西医对肌萎缩侧索硬化症病因病机的研究进展［J］.时珍国医国药，2015， 26（12）： 2990-2992.

YAMASHITA T， HIDEYAMA T， TERAMOTO S， et al. The abnormal processing of TDP-43 is not an upstream event of reduced ADAR2 activity in ALS motor neurons［J］. Neurosci Res， 2012， 73： 153-160.

宋玉，王恒，潘卫东，等. 从运动神经元的TDP-43蛋白表达和ADAR2活性探讨肌萎缩侧索硬化症的发病机制［J］. 中国临床神经科学，2014， 22（3）： 356-360.

BONIFACINO T， ZERBO R A， BALBI M， et al. Nearly 30 years of animal models to study amyotrophic lateral sclerosis：a historical overview and future perspectives［J］. Int J Mol Sci， 2021， 22（22）： 12236.

PAN H， WANG H， TAO Y， et al. Evidence-Based Research Strategy of Traditional Chinese Medicine for Amyotrophic Lateral Sclerosis［J］. Evid Based Complement Alternat Med， 2021， 2021： 3402753 .

BEUG S T， CHEUNG H H， LACASSE E C， et al. Modulation of immune signaling by inhibitors of apoptosis［J］. Trends Immunol， 2012， 33： 535-545.

ROSENBLUM L T， SHAMAMANDRI-M S， GHOSH B， et al. Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS［J］. Exp Neurol，2017， 292： 145-153.

ZHAO T， YE S， TANG Z， et al. Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish［J］. Cell Death Dis，2021， 12（2）： 151.

IACCARINO C， MURA M E， ESPOSITO S， et al. Bcl2-A1 interacts with pro-caspase-3： implications for amyotrophic lateral sclerosis［J］. Neurobiol Dis， 2011， 43： 642-650.

MORISON L M， CRAMER B E， CHEESMAN E J， et al. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia［J］. Nat Genet， 2008， 40： 387-389.

ZOU H， E H， KAMARAJ R， et al. A review on pharmacological activities and synergistic effect of quercetin with small molecule agents［J］. Phytomedicine， 2021， 92： 153736.

DEV K P， MALAR D S， NABAVI S F， et al. Kaempferol and inflammation： From chemistry to medicine［J］. Pharmacol Res， 2015， 99： 1-10.

LIU Z， YAO X， SUN B， et al. Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury［J］. Free Radic Biol Med， 2021， 168： 142-154.

ZHANG K， WANG H， QU D， et al. Luteolin alleviates methamphetamine-induced hepatotoxicity by suppressing the p53 pathway-mediated apoptosis，autophagy，and inflammation in rats［J］. Front Pharmacol，2021， 12： 641917.

RAINA R， PRAMODH S，RAIS N， et al. Luteolin inhibits proliferation， triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells［J］. Oncol Lett， 2021， 21（3）： 192.

Views

227

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Exploration on mechanism of Baitouweng Decoction against colorectal adenoma based on network pharmacology and experimental validation

Exploration on molecular mechanism of Fructus Psoraleae in treating lung adenocarcinoma based on network pharmacology and experimental pharmacology

Exploration on mechanism of Wuling Powder combined with Taohong Siwu Decoction in treatment of heart failure based on network pharmacology， molecular docking， and experimental validation

Literature mining and bioinformatics analysis of Xue Xue’s Medical Cases for differentiation and treatment of gastrointestinal diseases

Exploration on mechanism of Shaoyao Gancao Decoction in treating ulcerative colitis based on network pharmacology and in vitro cell experiments

Related Author

No data

Related Institution

Institute of Digestive Diseases， Longhua Hospital， Shanghai University of Traditional Chinese Medicine

Shanghai Pudong New Area Hospital of Traditional Chinese Medicine

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Shanghai Municipal Hospital of Traditional Chinese Medicine， Shanghai University of Traditional Chinese Medicine

Institute of Interdisciplinary Integrative Medicine Research， Shanghai University of Traditional Chinese Medicine

⁰