Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification

HUANG Shuai-yang; HOU Dan; HUANG Gui-rui; LYU Ming-sheng; GONG Xue-feng; ZHANG Shi-yu; ZHANG Zhi-jie; CUI Hong-sheng

doi:10.13422/j.cnki.syfjx.20220725

您当前的位置：

首页 >

文章列表页 >

Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification

更新时间：2023-05-17

- Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 9, Pages: 150-157(2022)
- 作者机构：
  
  1.北京中医药大学第三附属医院，北京 100029
  2.北京中医药大学，北京 100029
  3.首都医科大学附属北京朝阳医院，北京 100020
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220725
  CLC： R22;R242;R2-031;R285.5
- Received：20 November 2021，
  
  Published Online：07 February 2022，
  
  Published：05 May 2022
- 稿件说明：
移动端阅览
黄帅阳,候丹,黄贵锐等.基于网络药理学探讨哮喘宁颗粒治疗支气管哮喘的作用机制及PI3K/Akt信号通路验证[J].中国实验方剂学杂志,2022,28(09):150-157.

HUANG Shuai-yang,HOU Dan,HUANG Gui-rui,et al.Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(09):150-157.
黄帅阳,候丹,黄贵锐等.基于网络药理学探讨哮喘宁颗粒治疗支气管哮喘的作用机制及PI3K/Akt信号通路验证[J].中国实验方剂学杂志,2022,28(09):150-157. DOI： 10.13422/j.cnki.syfjx.20220725.

HUANG Shuai-yang,HOU Dan,HUANG Gui-rui,et al.Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(09):150-157. DOI： 10.13422/j.cnki.syfjx.20220725.

摘要

目的

基于网络药理学预测哮喘宁颗粒治疗支气管哮喘的潜在分子机制，并采用卵蛋白（OVA）致敏诱发的支气管哮喘大鼠模型对关键信号通路之一磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）进行实验验证。

方法

利用传统中药系统药理学数据库和分析平台（TCMSP）和中药分子机制生物信息学分析网络（BATMAN-TCM）筛选哮喘宁颗粒的主要有效成分和作用靶点。通过人类基因数据库（GeneCards）、人类孟德尔遗传靶点数据库（OMIM）等5个疾病数据库获取支气管哮喘相关的疾病靶点。筛选并通过韦恩图获得两者的共同靶标，使用蛋白相互作用数据库（STRING）构建化合物-疾病的蛋白质-蛋白质相互作用网络（PPI），并用Cytoscape 3.8.0建立“哮喘宁关键活性成分-核心靶基因”网络。通过基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。制备OVA刺激诱导的支气管哮喘大鼠模型，通过苏木素-伊红（HE）染色观察支气管与肺组织炎症情况，蛋白免疫印迹法（Western blot）实验验证网络药理学富集分析结果。

结果

该实验分别获取哮喘宁活性成分232个，相关靶点4 687个，收集哮喘宁与支气管哮喘的共同靶点233个，包括嗜酸性粒细胞衍生神经毒素1（EDN1）、环磷腺苷效应元件结合蛋白1（CREB1）、细胞周期蛋白依赖性激酶抑制剂1A（CDKN1A）、表皮生长因子受体（EGFR）、丝裂原活化蛋白激酶14（MAPK14）、Akt1等。KEGG通路分析筛选了186条相关信号通路，显示PI3K/Akt信号通路可能在哮喘宁治疗支气管哮喘的过程中起关键作用。动物实验表明，与哮喘模型组比较，哮喘宁组可明显减轻大鼠气道炎症反应和平滑肌增生，并明显下调PI3K、Akt蛋白表达（

0.05）。

结论

哮喘宁治疗哮喘具有多成分、多靶点、多通路协同作用的特点，其中哮喘宁可能通过调控PI3K/Akt信号通路相关基因的表达，进一步发挥抗炎症的药理效应，为后续深入研究哮喘宁治疗支气管哮喘的复杂机制提供了理论依据。

Abstract

Objective

To explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway on ovalbumin （OVA） sensitization-induced bronchial asthma model in rats.

Method

The main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man （OMIM）. The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction （PPI） network of "compound-disease"， and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes （"ingredient-gene" network）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin （HE） staining， and the enrichment analysis results of the network pharmacology were verified by Western blot.

Result

In this experiment， 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out， and 233 common targets of Xiaochuanning granules and bronchial asthma were collected， including eosinophil-derived neurotoxin 1 （EDN1）， cyclic AMP response element-binding protein 1 （CREB1）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 14 （MAPK14）， and Akt1. KEGG pathway analysis revealed 186 related signaling pathways， indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group （

0.05）.

Conclusion

Xiaochuanning granules have the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.

关键词

Keywords

references

HUANG K ， YANG T ， XU J ， et al . Prevalence，risk factors，and management of asthma in China：A national cross‐sectional study ［J］. Lancet ， 2019 ， 394 （ 10196 ）： 407 ‐ 418 .

STERN J ， PIER J ， LITONJUA A A . Asthma epidemiology and risk factors ［J］. Semin Immunopathol ， 2020 ， 42 （ 1 ）： 5 - 15 .

SOCKRIDER M ， FUSSNER L . What Is Asthma？［J］ Am J Respir Crit Care Med ， 2020 ， 202 （ 9 ）： p25 - p26 .

WANG Y ， CHEN Y J ， XIANG C ， et al . Discovery of potential asthma targets based on the clinical efficacy of traditional Chinese medicine formulas ［J］. J Ethnopharmacol ， 2020 ， 252 （ 24 ）： 112635 .

YAN S F ， YU T ， LI F S ， et al . Effectiveness and safety of 3 different traditional Chinese therapies for asthma in minors： A protocol for systematic review and network meta-analysis ［J］. Medicine （Baltimore）， 2020 ， 99 （ 47 ）： e23021 .

崔红生，武维屏，赵燕荣，等 . 哮喘宁煎剂治疗支气管哮喘急性发作期的临床研究［J］. 北京中医药大学学报， 1999 ， 22 （ 1 ）： 57 - 60

崔红生，黄启福，武维屏 . 哮喘宁煎剂对哮喘豚鼠模型气道嗜酸细胞浸润的影响［J］. 中华结核和呼吸杂志， 1999 ， 22 （ 8 ）： 495 - 496 .

LIU Z ， GUO F ， WANG Y ， et al . BATMAN-TCM： A bioinformatics analysis tool for molecular mechANism of mraditional Chinese medicine ［J］. Sci Rep ， 2016 ， 6 （ 16 ）： 21146 .

WAN Y ， XU L ， LIU Z ， et al . Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms ［J］. BMC Complement Altern Med ， 2019 ， 19 （ 1 ）： 158 .

LI X ， HE P ， HOU Y ， et al . Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes ［J］. Drug Dev Res ， 2019 ， 80 （ 5 ）： 637 - 645 .

LIU X ， LIU X ， QIAO T ， et al . Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis ［J］. Oncol Lett ， 2020 ， 9 （ 3 ）： 1881 - 1889 .

候丹，黄帅阳，吕明圣，等 . 桑梅止咳颗粒对咳嗽变异性哮喘大鼠气道炎症反应的作用及机制［J］. 中国实验方剂学杂志， 2022 ， 28 （ 2 ）： 62 - 66 .

单敏敏，李长安，崔红生 . 哮喘宁颗粒对哮喘大鼠白三烯B4、白三烯C4、C-反应蛋白表达的调节作用［J］. 世界中西医结合杂志， 2019 ， 14 （ 1 ）： 1 - 3，12 .

FEHRENBACH H ， WAGNER C ， WEGMANN M . Airway remodeling in asthma： What really matters ［J］. Cell Tissue Res ， 2017 ， 367 （ 3 ）： 551 - 569 .

李竹英，陈璐，王丽洁 . 中药药对治疗支气管哮喘的研究进展［J］. 长春中医药大学学报， 2021 ， 37 （ 2 ）： 451 - 455 .

武维屏，崔红生 . 试论支气管哮喘从肝论治的生理病理学基础［J］. 中国中医基础医学杂志， 2002 ， 8 （ 10 ）： 7 - 8 .

崔红生，靳锐锋，田彦 . 情志因素与支气管哮喘证治探析［J］. 中华中医药杂志， 2014 ， 29 （ 3 ）： 771 - 773 .

单敏敏，李长安，崔红生 . 哮喘宁颗粒对哮喘大鼠Th1/Th2平衡和STAT1通路调节作用的研究［J］. 中国医药导报， 2019 ， 16 （ 10 ）： 11 - 15 .

MA B ， ATHARI S S ， MEHRABI NASAB E ， et al . PI3K/Akt/mTOR and TLR4/MyD88/NF- κ B signaling inhibitors attenuate pathological mechanisms of allergic asthma ［J］. Inflammation ， 2021 ， 44 （ 5 ）： 1895 - 1907 .

ATHARI S S . Targeting cell signaling in allergic asthma ［J］. Signal Transduct Target Ther ， 2019 ， 4 （ 1 ）： 1 - 19 .

赵革，张丹，杨小会，等 . 丁香活性组分抑制PI3K/Akt/mTOR通路诱导人结肠癌HCT116细胞凋亡的研究［J］. 中国中药杂志， 2021 ， 46 （ 5 ）： 1197 - 1204 .

刘小虎，赵志慧，周玥，等 . PI3K/Akt/mTOR自噬通路在人参皂苷Rg 1 延缓D-gal诱导的卵巢早衰小鼠模型卵巢早衰中的作用［J］. 中国中药杂志， 2020 ， 45 （ 24 ）： 6036 - 6042 .

PAN J ， YANG Q ， ZHOU Y ， et al . MicroRNA-221 modulates airway remodeling via the PI3K/Akt pathway in OVA-induced chronic murine asthma ［J］. Front Cell Dev Biol ， 2020 ， 8 （ 495 ）： 1 - 10 .

CURNOCK A P ， LOGAN M K ， WARD S G . Chemokine signalling： Pivoting around multiple phosphoinositide 3-kinases ［J］. Immunology ， 2002 ， 105 （ 2 ）： 125 - 136 .

WU D ， LI S ， LIU X ， et al . Alpinetin prevents inflammatory responses in OVA-induced allergic asthma through modulating PI3K/AKT/NF- κ B and HO-1 signaling pathways in mice ［J］. Int Immunopharmacol ， 2020 ， 89 （ Pt A ）： 1 - 11 .

ELLIOT J G ， NOBLE P B ， MAUAD T ， et al . Inflammation-dependent and independent airway remodelling in asthma ［J］. Respirology ， 2018 ， 23 （ 12 ）： 1138 - 1145 .

SOBIERAJ D M ， WEEDA E R ， NGUYEN E ， et al . Association of inhaled corticosteroids and long-acting β -agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma： A systematic review and Meta-analysis ［J］. JAMA ， 2018 ， 319 （ 14 ）： 1485 - 1496 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of Cordyceps in Treating Bronchial Asthma and Chronic Renal Failure with Concept of “Same Treatment for Different Diseases” Based on Network Pharmacology and Molecular Docking Technology

Clinical Efficacy and Mechanism of Compound Langdu Tincture in Treating Multiple Palmoplantar Warts of Dampness-toxin Accumulation Type

Excavation of New Prescription for Chronic Atrophic Gastritis and Its Verification of Syndrome Type of Deficiency of Stomach Yin

Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway

Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure

Related Author

Wen-jing LIAN

Jun HU

Meng-wei FU

Jin-lei LIU

Yong-mei LIU

Jie WANG

ZHENG Yuping

ZHANG Yanfeng

Related Institution

Guang'anmen Hospital China Academy Chinese Medical Sciences

The First Affiliated Hospital of Zhejiang Chinese Medical University （Zhejiang Provincial Hospital of Chinese Medicine）

Shanghai Pudong New Area Guangming Traditional Chinese Medicine（TCM） Hospital

Shuguang Hospital Affiliated to Shanghai University of TCM

College of Traditional Chinese Medicine， Xinjiang Medical University

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰