Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis
Abstract Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57796-3 |
| _version_ | 1797233637659246592 |
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| author | Qi Dong Guoxia Ren Yanzhao Li Dingjun Hao |
| author_facet | Qi Dong Guoxia Ren Yanzhao Li Dingjun Hao |
| author_sort | Qi Dong |
| collection | DOAJ |
| description | Abstract Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein–protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP. |
| first_indexed | 2024-04-24T16:19:20Z |
| format | Article |
| id | doaj.art-ff4319bd05d7487d96e21a6743e06884 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T16:19:20Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ff4319bd05d7487d96e21a6743e068842024-03-31T11:17:24ZengNature PortfolioScientific Reports2045-23222024-03-0114111110.1038/s41598-024-57796-3Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosisQi Dong0Guoxia Ren1Yanzhao Li2Dingjun Hao3Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Physical Medicine and Rehabilitation, Xi’an Chest HospitalDepartment of Traditional Chinese Medicine, First Clinical Medical College, Shaanxi University of Chinese MedicineDepartment of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein–protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.https://doi.org/10.1038/s41598-024-57796-3KaempferolOsteoporosisNetwork pharmacologyMolecular dockingIn vitro validation |
| spellingShingle | Qi Dong Guoxia Ren Yanzhao Li Dingjun Hao Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis Scientific Reports Kaempferol Osteoporosis Network pharmacology Molecular docking In vitro validation |
| title | Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| title_full | Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| title_fullStr | Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| title_full_unstemmed | Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| title_short | Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| title_sort | network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis |
| topic | Kaempferol Osteoporosis Network pharmacology Molecular docking In vitro validation |
| url | https://doi.org/10.1038/s41598-024-57796-3 |
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