Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis
Su Yuan,1,2 Biao Zuo,2,3 Si-Cong Zhou,1,2 Meng Wang,2,3 Kai-Yue Tan,2,3 Zhi-Wei Chen,2,3 Wen-Fu Cao1– 3 1Department of Combination of Chinese and Western Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Tradi...
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Dove Medical Press
2023-04-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/integrating-network-pharmacology-and-experimental-validation-to-explor-peer-reviewed-fulltext-article-DDDT |
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| author | Yuan S Zuo B Zhou SC Wang M Tan KY Chen ZW Cao WF |
| author_facet | Yuan S Zuo B Zhou SC Wang M Tan KY Chen ZW Cao WF |
| author_sort | Yuan S |
| collection | DOAJ |
| description | Su Yuan,1,2 Biao Zuo,2,3 Si-Cong Zhou,1,2 Meng Wang,2,3 Kai-Yue Tan,2,3 Zhi-Wei Chen,2,3 Wen-Fu Cao1– 3 1Department of Combination of Chinese and Western Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wen-Fu Cao, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email caowenfu20220401@163.comPurpose: 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.Keywords: astragaloside IV, pulmonary fibrosis, network pharmacology, cellular senescence, epithelial-mesenchymal transition |
| first_indexed | 2024-04-09T15:36:00Z |
| format | Article |
| id | doaj.art-df6cb359afa24936874f355581afae45 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-09T15:36:00Z |
| publishDate | 2023-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-df6cb359afa24936874f355581afae452023-04-27T19:02:47ZengDove Medical PressDrug Design, Development and Therapy1177-88812023-04-01Volume 171289130283344Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary FibrosisYuan SZuo BZhou SCWang MTan KYChen ZWCao WFSu Yuan,1,2 Biao Zuo,2,3 Si-Cong Zhou,1,2 Meng Wang,2,3 Kai-Yue Tan,2,3 Zhi-Wei Chen,2,3 Wen-Fu Cao1– 3 1Department of Combination of Chinese and Western Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wen-Fu Cao, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email caowenfu20220401@163.comPurpose: 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.Keywords: astragaloside IV, pulmonary fibrosis, network pharmacology, cellular senescence, epithelial-mesenchymal transitionhttps://www.dovepress.com/integrating-network-pharmacology-and-experimental-validation-to-explor-peer-reviewed-fulltext-article-DDDTastragaloside ivpulmonary fibrosisnetwork pharmacologycellular senescenceepithelial-mesenchymal transition |
| spellingShingle | Yuan S Zuo B Zhou SC Wang M Tan KY Chen ZW Cao WF Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis Drug Design, Development and Therapy astragaloside iv pulmonary fibrosis network pharmacology cellular senescence epithelial-mesenchymal transition |
| title | Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis |
| title_full | Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis |
| title_fullStr | Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis |
| title_full_unstemmed | Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis |
| title_short | Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis |
| title_sort | integrating network pharmacology and experimental validation to explore the pharmacological mechanism of astragaloside iv in treating bleomycin induced pulmonary fibrosis |
| topic | astragaloside iv pulmonary fibrosis network pharmacology cellular senescence epithelial-mesenchymal transition |
| url | https://www.dovepress.com/integrating-network-pharmacology-and-experimental-validation-to-explor-peer-reviewed-fulltext-article-DDDT |
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