Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis
Exocarpium Citri Grandis (ECG), a precious traditional Chinese medicine (TCM), has been widely utilized to improve the symptoms of chronic bronchitis (CB) such as cough or sputum. However, its underlying pharmacological mechanisms remain unclear. To investigate the potential mechanisms of ECG for th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223008900 |
| _version_ | 1797390492146597888 |
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| author | Jiawen Huang Zaibin Xu Jiayu Li Xinqian He Xinan Huang Xiaoling Shen Zhuohui Luo |
| author_facet | Jiawen Huang Zaibin Xu Jiayu Li Xinqian He Xinan Huang Xiaoling Shen Zhuohui Luo |
| author_sort | Jiawen Huang |
| collection | DOAJ |
| description | Exocarpium Citri Grandis (ECG), a precious traditional Chinese medicine (TCM), has been widely utilized to improve the symptoms of chronic bronchitis (CB) such as cough or sputum. However, its underlying pharmacological mechanisms remain unclear. To investigate the potential mechanisms of ECG for the treatment of CB, a comprehensive systems pharmacology strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and molecular biology experiments in vitro was carried out. In this study, 46 potential targets of CB screened for 10 active ingredients of ECG were strongly linked to inflammatory responses, immune processes, and apoptosis. Molecular docking revealed that the active ingredients of ECG have high binding activity for MyD88, NF-κB p65, Caspase9, and Caspase3, respectively. Meanwhile, MD simulations confirmed that neohesperidin and naringenin have high stability and low binding free energy with NF-κB p65 and Caspase3 in the binding pocket. In the LPS-induced RAW264.7 cell inflammatory model, ECG markedly reduced the secretion of IL1β, IL6, TNF-α, and NO. Transcriptomics showed a total of 337 differential expression genes (DEGs) were screened after ECG treatment, of which 233 down-regulated DEGs were closely associated with the NF-κ B signaling pathway, the Toll-like receptor signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. Further analysis results revealed that ECG significantly down-regulated the expression of TLR4, MyD88, NF-κB p65, NF-κB p-p65 (S536), p-IκBα (S36), COX2, ICAM1, and iNOS, and up-regulated the expression of IκBα, inhibited NF-κB p65 entry into the nucleus, thereby suppressing NF-κB signaling transduction. Furthermore, ECG also significantly up-regulated the expression of Bcl-2 and down-regulated the expression of Bax, Caspase3, Caspase8, and Caspase9, inhibiting apoptosis in a dose-dependent manner. Our study reveals the potential pharmacological mechanisms of ECG for the treatment of CB and provides a scientific basis for its clinical application. |
| first_indexed | 2024-03-08T23:12:37Z |
| format | Article |
| id | doaj.art-898f2e1d91ff4d818d02b560e3cc1091 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-08T23:12:37Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-898f2e1d91ff4d818d02b560e3cc10912023-12-15T07:23:30ZengElsevierArabian Journal of Chemistry1878-53522024-01-01171105428Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitisJiawen Huang0Zaibin Xu1Jiayu Li2Xinqian He3Xinan Huang4Xiaoling Shen5Zhuohui Luo6Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, ChinaArtemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510422, ChinaArtemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510422, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Corresponding authors.Honz Pharmaceutical Co., Ltd., Haikou 570311, China; Hainan Pharmaceutical Research and Development Science Park, Haikou 571199, China; Research Center for Drug Safety Evaluation of Hainan Province, Hainan Medical University, Haikou 571199, China; Corresponding authors.Exocarpium Citri Grandis (ECG), a precious traditional Chinese medicine (TCM), has been widely utilized to improve the symptoms of chronic bronchitis (CB) such as cough or sputum. However, its underlying pharmacological mechanisms remain unclear. To investigate the potential mechanisms of ECG for the treatment of CB, a comprehensive systems pharmacology strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and molecular biology experiments in vitro was carried out. In this study, 46 potential targets of CB screened for 10 active ingredients of ECG were strongly linked to inflammatory responses, immune processes, and apoptosis. Molecular docking revealed that the active ingredients of ECG have high binding activity for MyD88, NF-κB p65, Caspase9, and Caspase3, respectively. Meanwhile, MD simulations confirmed that neohesperidin and naringenin have high stability and low binding free energy with NF-κB p65 and Caspase3 in the binding pocket. In the LPS-induced RAW264.7 cell inflammatory model, ECG markedly reduced the secretion of IL1β, IL6, TNF-α, and NO. Transcriptomics showed a total of 337 differential expression genes (DEGs) were screened after ECG treatment, of which 233 down-regulated DEGs were closely associated with the NF-κ B signaling pathway, the Toll-like receptor signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. Further analysis results revealed that ECG significantly down-regulated the expression of TLR4, MyD88, NF-κB p65, NF-κB p-p65 (S536), p-IκBα (S36), COX2, ICAM1, and iNOS, and up-regulated the expression of IκBα, inhibited NF-κB p65 entry into the nucleus, thereby suppressing NF-κB signaling transduction. Furthermore, ECG also significantly up-regulated the expression of Bcl-2 and down-regulated the expression of Bax, Caspase3, Caspase8, and Caspase9, inhibiting apoptosis in a dose-dependent manner. Our study reveals the potential pharmacological mechanisms of ECG for the treatment of CB and provides a scientific basis for its clinical application.http://www.sciencedirect.com/science/article/pii/S1878535223008900Exocarpium Citri GrandisChronic bronchitisNetwork pharmacologyMolecular dockingMolecular dynamics simulationTranscriptomics |
| spellingShingle | Jiawen Huang Zaibin Xu Jiayu Li Xinqian He Xinan Huang Xiaoling Shen Zhuohui Luo Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis Arabian Journal of Chemistry Exocarpium Citri Grandis Chronic bronchitis Network pharmacology Molecular docking Molecular dynamics simulation Transcriptomics |
| title | Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis |
| title_full | Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis |
| title_fullStr | Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis |
| title_full_unstemmed | Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis |
| title_short | Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis |
| title_sort | systems pharmacology based dissection of potential mechanisms of exocarpium citri grandis for the treatment of chronic bronchitis |
| topic | Exocarpium Citri Grandis Chronic bronchitis Network pharmacology Molecular docking Molecular dynamics simulation Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223008900 |
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