Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD
Abstract Hesperetin (HE), a natural flavonoid exhibiting anti-inflammatory and antioxidant properties, holds significant potential in treating chronic obstructive pulmonary disease (COPD). Nonetheless, the precise mechanisms underlying its effects are yet to be fully elucidated. In this study, we ai...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-95810-4 |
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| author | Jingxi Wang Hongyang Wang Xin Kang Xiaotian Wang Xi Li Jie Guo Xuan Jing Xi Chu Xue Han |
| author_facet | Jingxi Wang Hongyang Wang Xin Kang Xiaotian Wang Xi Li Jie Guo Xuan Jing Xi Chu Xue Han |
| author_sort | Jingxi Wang |
| collection | DOAJ |
| description | Abstract Hesperetin (HE), a natural flavonoid exhibiting anti-inflammatory and antioxidant properties, holds significant potential in treating chronic obstructive pulmonary disease (COPD). Nonetheless, the precise mechanisms underlying its effects are yet to be fully elucidated. In this study, we aim to explore the role and potential mechanism of HE in treating COPD using network pharmacology, molecular docking and experimental validation. We screened for HE and COPD-related targets from public databases, and then imported potential targets into a STRING database to establish a protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis were performed to obtain key signaling pathways. We then predicted the binding interactions between HE and core targets using molecular docking. The animal model of COPD was established through lipopolysaccharide and cigarette smoke induction in mice to observe lung function, inflammatory factors, pathology, and the expression of related proteins. Network pharmacology findings unveiled that HE and COPD shared 105 common targets. MAPKs and NF-κB signaling pathways were selected for further validation. In animal experiment, HE enhanced lung function and histopathological morphology, while reducing inflammation levels. The results of Western blot tests indicated that HE treatment considerably inhibited the expression of MAPKs and NF-κB. HE effectively reduced lung inflammation and improved lung function in mice. This mechanism may be achieved by inhibition of MAPKs and NF-κB signaling pathways. |
| format | Article |
| id | doaj-art-6226ae4c850f4bec82ad08ebab4ca034 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6226ae4c850f4bec82ad08ebab4ca0342025-08-20T01:54:19ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-95810-4Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPDJingxi Wang0Hongyang Wang1Xin Kang2Xiaotian Wang3Xi Li4Jie Guo5Xuan Jing6Xi Chu7Xue Han8The First Affiliated Hospital, Hebei University of Chinese MedicineHebei University of Chinese MedicineThe First Affiliated Hospital, Hebei University of Chinese MedicineThe First Affiliated Hospital, Hebei University of Chinese MedicineThe First Affiliated Hospital, Hebei University of Chinese MedicineThe First Affiliated Hospital, Hebei University of Chinese MedicineThe First Affiliated Hospital, Hebei University of Chinese MedicineThe Fourth Hospital of Hebei Medical UniversitySchool of Pharmacy, Hebei University of Chinese MedicineAbstract Hesperetin (HE), a natural flavonoid exhibiting anti-inflammatory and antioxidant properties, holds significant potential in treating chronic obstructive pulmonary disease (COPD). Nonetheless, the precise mechanisms underlying its effects are yet to be fully elucidated. In this study, we aim to explore the role and potential mechanism of HE in treating COPD using network pharmacology, molecular docking and experimental validation. We screened for HE and COPD-related targets from public databases, and then imported potential targets into a STRING database to establish a protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis were performed to obtain key signaling pathways. We then predicted the binding interactions between HE and core targets using molecular docking. The animal model of COPD was established through lipopolysaccharide and cigarette smoke induction in mice to observe lung function, inflammatory factors, pathology, and the expression of related proteins. Network pharmacology findings unveiled that HE and COPD shared 105 common targets. MAPKs and NF-κB signaling pathways were selected for further validation. In animal experiment, HE enhanced lung function and histopathological morphology, while reducing inflammation levels. The results of Western blot tests indicated that HE treatment considerably inhibited the expression of MAPKs and NF-κB. HE effectively reduced lung inflammation and improved lung function in mice. This mechanism may be achieved by inhibition of MAPKs and NF-κB signaling pathways.https://doi.org/10.1038/s41598-025-95810-4Chronic obstructive pulmonary diseaseHesperetinNetwork pharmacologyMolecular dockingMAPKs/NF-κB signaling pathway |
| spellingShingle | Jingxi Wang Hongyang Wang Xin Kang Xiaotian Wang Xi Li Jie Guo Xuan Jing Xi Chu Xue Han Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD Scientific Reports Chronic obstructive pulmonary disease Hesperetin Network pharmacology Molecular docking MAPKs/NF-κB signaling pathway |
| title | Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD |
| title_full | Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD |
| title_fullStr | Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD |
| title_full_unstemmed | Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD |
| title_short | Integrated network pharmacology, molecular docking, and animal experiments to reveal the potential mechanism of hesperetin on COPD |
| title_sort | integrated network pharmacology molecular docking and animal experiments to reveal the potential mechanism of hesperetin on copd |
| topic | Chronic obstructive pulmonary disease Hesperetin Network pharmacology Molecular docking MAPKs/NF-κB signaling pathway |
| url | https://doi.org/10.1038/s41598-025-95810-4 |
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