Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment

Shuaiyang HUANG; Jiamei WANG; Guirui HUANG; Xuefeng GONG; Mingsheng LYU; Dan HOU; Hongsheng CUI

doi:10.13422/j.cnki.syfjx.20221322

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Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment

更新时间：2022-08-11

- Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 18, Pages: 169-176(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.山西省人民医院，太原 030012
  4.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.20221322
  CLC： R22;R242;R2-031;R285.5
- Published：20 September 2022，
  
  Published Online：19 April 2022，
  
  Received：26 January 2022，
- 稿件说明：
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黄帅阳,王佳美,黄贵锐等.基于网络药理学探讨保肺康颗粒对肺纤维化大鼠模型PI3K/Akt信号通路的调节作用[J].中国实验方剂学杂志,2022,28(18):169-176.

HUANG Shuaiyang,WANG Jiamei,HUANG Guirui,et al.Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):169-176.
黄帅阳,王佳美,黄贵锐等.基于网络药理学探讨保肺康颗粒对肺纤维化大鼠模型PI3K/Akt信号通路的调节作用[J].中国实验方剂学杂志,2022,28(18):169-176. DOI： 10.13422/j.cnki.syfjx.20221322.

HUANG Shuaiyang,WANG Jiamei,HUANG Guirui,et al.Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):169-176. DOI： 10.13422/j.cnki.syfjx.20221322.

摘要

目的

基于网络药理学及动物实验验证的方法探讨保肺康颗粒（保肺康）对治疗肺纤维化的作用靶点及机制。

方法

借助相关中药药理学数据库和分析平台筛选保肺康的有效成分及靶点；于各疾病数据库中检索肺间质纤维化疾病相关靶点，提取保肺康与肺纤维化的共同靶点，利用蛋白相互作用数据库（STRING）构建蛋白质-蛋白质相互作用（PPI）网络，通过Cytoscape 3.8.0软件对关键靶点进行网络拓扑学分析，建立“保肺康关键活性成分-核心靶基因”网络，对核心靶基因进行基因本体（GO）及京都基因与基因组百科全书（KEGG）富集分析以探究保肺康治疗肺纤维化可能的分子机制。以博来霉素气管滴注的方式建立肺间质纤维化大鼠模型，分为正常组、模型组、保肺康组（27.18 g·kg

-1

）、醋酸泼尼松组（1.17 mg·kg

-1

），灌胃21 d，对各组肺组织用苏木素-伊红（HE）染色进行形态学观察，运用免疫组化（IHC）对大鼠肺组织内的磷脂酰肌醇3-激酶（PI3K）和蛋白激酶B（Akt）蛋白进行检测。

结果

网络药理学方法筛选出保肺康治疗肺间质纤维化疾病关键基因18个，包括Akt1、丝裂原活化蛋白激酶1（MAPK1）、核蛋白类癌基因（MYC）、低氧诱导因子-1

（HIF-1

）重组蛋白、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）、核心结合因子2（RUNX2）等。KEGG富集分析预测保肺康主要是通过PI3K/Akt信号通路、肿瘤坏死因子（TNF）信号通路、白细胞介素-17（IL-17）信号通路等发挥抗纤维化作用。IHC结果显示，与模型组比较，保肺康组内PI3K、Akt蛋白表达均明显降低（

0.05，

0.01）。

结论

保肺康在治疗肺纤维化上具有毒性低、多层次、多靶点的特点，其可能通过调控PI3K/Akt信号通路影响肺纤维化程度，从而达到改善肺功能的作用。

Abstract

Objective

To investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment.

Method

The active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining.

Result

Based on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1

（HIF-1

）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （

0.05，

0.01）.

Conclusion

Baofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.

关键词

保肺康颗粒网络药理学肺纤维化实验验证磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）信号通路

Keywords

Baofeikang granulesnetwork pharmacologypulmonary fibrosisexperimental verificationphosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway

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