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| Autori principali: | , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
| Pubblicazione: |
International journal of molecular sciences
2025
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| Soggetti: | |
| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/39940967/ |
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| _version_ | 1868266244700897282 |
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| author | Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing |
| author_facet | Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing |
| collection | PubMed - marine biology |
| contents | Network Pharmacology Analysis and Biological Validation Systemically Identified the Active Ingredients and Molecular Targets of Kudzu Root on Osteoporosis. Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing Animals Zebrafish Network Pharmacology Pueraria Osteoporosis Molecular Docking Simulation Protein Interaction Maps Plant Roots Molecular Dynamics Simulation Signal Transduction Disease Models, Animal Plant Extracts Humans As a traditional medicinal food, Kudzu root (KR) has been proven to be an effective medicine for treating osteoporosis (OP). However, its precise targets and underlying integrated pharmacological mechanisms on OP have not yet been systematically investigated. The aim of the present study was to systemically explore the active ingredients, molecular targets, and ingredient-target network of KR against OP by the methods of network pharmacology followed by biological validation in a glucocorticoid-induced bone loss model of zebrafish. Our results identified a total of 15 active compounds with good pharmacokinetic properties in KR and 119 targets related to OP from correspondent databases, forming an ingredient-target network. Additionally, the protein-protein interaction (PPI) network further identified 39 core targets. Enrichment analyses with functional annotation revealed that the TNF signaling pathway and osteoclast differentiation process were significantly enriched by multi-targets including AKT1, P65, MAPK14, JUN, TNF-α, MMP9, IL6, and IL1B, etc., and served as the critical targets for molecular docking, molecular dynamics simulation, and in vivo experiment validation. These critical targets performed effectively in molecular docking and molecular dynamics, with AKT1, MMP9, and TNF-α exhibiting more prominent binding energy with Coumestrol, Genistein, and Genistein 7-glucoside, respectively. Further experimental validation in a zebrafish model indicated that KR could regulate the expressions of critical targets (AKT1, P65, MAPK14, JUN, TNF-α, and MMP9). This study provides a systemic perspective of the relationships between the active ingredients of KR and their multi-targets in OP, thereby constructing a pharmacological network to clarify the mechanisms by which KR ameliorates OP. |
| format | Artículo científico |
| id | pubmed_39940967 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | International journal of molecular sciences |
| record_format | pubmed |
| spellingShingle | Network Pharmacology Analysis and Biological Validation Systemically Identified the Active Ingredients and Molecular Targets of Kudzu Root on Osteoporosis. Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing Animals Zebrafish Network Pharmacology Pueraria Osteoporosis Molecular Docking Simulation Protein Interaction Maps Plant Roots Molecular Dynamics Simulation Signal Transduction Disease Models, Animal Plant Extracts Humans Network Pharmacology Analysis and Biological Validation Systemically Identified the Active Ingredients and Molecular Targets of Kudzu Root on Osteoporosis. Liu, Zhi-Wen Zhang, Bo-Bo Kwok, Kevin Wing-Hin Dong, Xiao-Li Wong, Ka-Hing Animals Zebrafish Network Pharmacology Pueraria Osteoporosis Molecular Docking Simulation Protein Interaction Maps Plant Roots Molecular Dynamics Simulation Signal Transduction Disease Models, Animal Plant Extracts Humans As a traditional medicinal food, Kudzu root (KR) has been proven to be an effective medicine for treating osteoporosis (OP). However, its precise targets and underlying integrated pharmacological mechanisms on OP have not yet been systematically investigated. The aim of the present study was to systemically explore the active ingredients, molecular targets, and ingredient-target network of KR against OP by the methods of network pharmacology followed by biological validation in a glucocorticoid-induced bone loss model of zebrafish. Our results identified a total of 15 active compounds with good pharmacokinetic properties in KR and 119 targets related to OP from correspondent databases, forming an ingredient-target network. Additionally, the protein-protein interaction (PPI) network further identified 39 core targets. Enrichment analyses with functional annotation revealed that the TNF signaling pathway and osteoclast differentiation process were significantly enriched by multi-targets including AKT1, P65, MAPK14, JUN, TNF-α, MMP9, IL6, and IL1B, etc., and served as the critical targets for molecular docking, molecular dynamics simulation, and in vivo experiment validation. These critical targets performed effectively in molecular docking and molecular dynamics, with AKT1, MMP9, and TNF-α exhibiting more prominent binding energy with Coumestrol, Genistein, and Genistein 7-glucoside, respectively. Further experimental validation in a zebrafish model indicated that KR could regulate the expressions of critical targets (AKT1, P65, MAPK14, JUN, TNF-α, and MMP9). This study provides a systemic perspective of the relationships between the active ingredients of KR and their multi-targets in OP, thereby constructing a pharmacological network to clarify the mechanisms by which KR ameliorates OP. |
| title | Network Pharmacology Analysis and Biological Validation Systemically Identified the Active Ingredients and Molecular Targets of Kudzu Root on Osteoporosis. |
| topic | Animals Zebrafish Network Pharmacology Pueraria Osteoporosis Molecular Docking Simulation Protein Interaction Maps Plant Roots Molecular Dynamics Simulation Signal Transduction Disease Models, Animal Plant Extracts Humans |
| url | https://pubmed.ncbi.nlm.nih.gov/39940967/ |