Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis

作者全名："Yuan, Su; Zuo, Biao; Zhou, Si-Cong; Wang, Meng; Tan, Kai-Yue; Chen, Zhi-Wei; Cao, Wen-Fu"

作者地址："[Yuan, Su; Zhou, Si-Cong; Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, Dept Combinat Chinese & Western Med, Chongqing, Peoples R China; [Yuan, Su; Zuo, Biao; Zhou, Si-Cong; Wang, Meng; Tan, Kai-Yue; Chen, Zhi-Wei; Cao, Wen-Fu] Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing, Peoples R China; [Zuo, Biao; Wang, Meng; Tan, Kai-Yue; Chen, Zhi-Wei; Cao, Wen-Fu] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing, Peoples R China; [Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Cao, WF (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：DRUG DESIGN DEVELOPMENT AND THERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000982122500001

JCR分区：Q1

影响因子：4.7

年份：2023

卷号：17

期号：　

开始页：1289

结束页：1302

文献类型：Article

关键词：astragaloside IV; pulmonary fibrosis; network pharmacology; cellular senescence; epithelial-mesenchymal transition

摘要："Purpose: Our study aims to reveal the pharmacological mechanism of Astragaloside IV in the treatment of pulmonary fibrosis(PF) through network pharmacology and experimental validation. Methods: We first determined the in vivo anti-pulmonary fibrosis effect of Astragaloside IV by HE, MASSON staining, and lung coefficients, then used network pharmacology to predict the signaling pathways and molecularly docked key pathway proteins, and finally validated the results by in vivo and in vitro experiments. Results: In in vivo experiments, we found that Astragaloside IV improved body weight (P < 0.05), increased lung coefficients (P < 0.05), and reduced lung inflammation and collagen deposition in mice with pulmonary fibrosis. The network pharmacology results showed that Astragaloside IV had 104 cross-targets with idiopathic pulmonary fibrosis, and the results of KEGG enrichment analysis indicated that cellular senescence could be an important pathway for Astragaloside IV in the treatment of pulmonary fibrosis. Astragaloside IV also bound well to senescence-associated proteins, according to molecular docking results. The results of both in vivo and in vitro experiments showed that Astragaloside IV significantly inhibited senescence protein markers such as P53, P21, and P16 and delayed cellular senescence (P < 0.05). In in vivo experiments, we also found that Astragaloside IV reduced the production of SASPs (P < 0.05), and in in vitro experiments, Astragaloside IV also reduced the production of ROS. In addition, by detecting epithelial-mesenchymal transition (EMT)-related marker protein expression, we also found that Astragaloside IV significantly inhibited the development of EMT in both in vivo and in vitro experiments (P < 0.05). Conclusion: Our research found that Astragaloside IV could alleviate bleomycin-induced PF by preventing cellular senescence and EMT."

基金机构："National Natural Science Foundation of China [81573860, 82004168]; Natural Science Foundation Project of Chongqing [cstc2019jcyj-msxmX0180]; Kewei Joint Research Project of Chongqing [2019ZY3503]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 81573860, No. 82004168) , Natural Science Foundation Project of Chongqing (Grant No. cstc2019jcyj-msxmX0180) , Kewei Joint Research Project of Chongqing (Grant No. 2019ZY3503) . We thank the authors for the development of the database and software used in this paper, we also thank Figdraw ( www.figdraw.com ) for the assistance in creating flow chart."