Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models
1Ganzhou Key Laboratory for Drug Screening and Discovery, Gannan Normal University, Ganzhou 341000, China.
Abstract:
Since osteoporosis critically influences the lives of patients with a high incidence, effective therapeutic treatments are important. Quercetin has been well recognized as a bone-sparing agent and thus the underlying mechanisms warrant further investigation. In the current study, the network pharmacology strategy and zebrafish model were utilized to explain the potential pharmacological effects of quercetin on osteoporosis. The potential targets and related signaling pathways were explored through overlapping target prediction, protein-protein interaction network construction, and functional enrichment analysis. Furthermore, we performed docking studies to verify the specific interactions between quercetin and crucial targets. Consequently, 55 targets were related to osteoporosis disease among the 159 targets of quercetin obtained by three database sources. Thirty hub targets were filtered through the cytoNCA plugin. Additionally, the Gene Ontology functions in the top 10 respective biological processes, molecular functions, and cell components as well as the top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were depicted. The most significance difference in the KEGG pathways was the TNF signaling pathway, consisting of the Nuclear Factor Kappa B Subunit (NF-κB), Extracellular Regulated Protein Kinases (ERK) 1/2, Activator Protein 1 (AP-1), Interleukin 6 (IL6), Transcription factor AP-1 (Jun), and Phosphatidylinositol 3 Kinase (PI3K), which were probably involved in the pharmacological effects. Moreover, molecular docking studies revealed that the top three entries were Interleukin 1 Beta (IL1B), the Nuclear Factor NF-Kappa-B p65 Subunit (RelA), and the Nuclear Factor Kappa B Subunit 1 (NFKB1), respectively. Finally, these results were verified by alizarin red-stained mineralized bone in zebrafish and related qPCR experiments. The findings probably facilitate the mechanism elucidation related to quercetin anti-osteoporosis action.
Insights
Quercetin shows potential for treating osteoporosis by influencing key targets and pathways like TNF signaling. This study used network pharmacology and zebrafish models to uncover its bone-sparing mechanisms.
Area of Science:
- Pharmacology
- Biochemistry
- Genetics
Background:
- Osteoporosis is a significant health concern requiring effective treatments.
- Quercetin is recognized for its bone-sparing properties, but its mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the pharmacological mechanisms of quercetin in treating osteoporosis using network pharmacology and a zebrafish model.
- To identify key targets and signaling pathways involved in quercetin's anti-osteoporosis effects.
Main Methods:
- Network pharmacology strategy including target prediction, protein-protein interaction network construction, and functional enrichment analysis.
- Molecular docking studies to validate quercetin-target interactions.
- In vivo validation using a zebrafish model with alizarin red staining and qPCR.
Main Results:
- Identified 55 osteoporosis-related targets for quercetin out of 159 total targets.
- Thirty hub targets were identified, with the TNF signaling pathway highlighted.
- Key molecules in the TNF pathway include Nuclear Factor Kappa B Subunit (NF-κB), ERK1/2, AP-1, IL6, Jun, and PI3K.
- Molecular docking confirmed interactions with IL1B, RelA, and NFKB1.
- Zebrafish experiments validated quercetin's effect on bone mineralization.
Conclusions:
- Quercetin likely exerts anti-osteoporosis effects through modulation of the TNF signaling pathway and interaction with key proteins.
- This study provides a mechanistic basis for quercetin's therapeutic potential in osteoporosis.
- Findings facilitate further research into quercetin-based osteoporosis treatments.
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