The potential pharmacological mechanism of prunetin against osteoporosis: transcriptome analysis, molecular docking, and experimental approaches

Abstract

Background

Prunetin is an O-methylated isoflavone, known for its beneficial properties. However, its specific pharmacological effects in the treatment of osteoporosis (OP) remain poorly understood. This study aims to elucidate the mechanisms underlying the antiosteoporotic effects of prunetin through a combination of bioinformatics analysis and cell experiments.

Methods

We gathered predicted targets of prunetin from various online platforms. Differential expression analysis of mRNAs in patients with OP was conducted using the Limma package, based on the GSE35959 dataset. A PPI network diagram was visualized and analyzed using Cytoscape 3.7.2 software. Molecular docking was employed to assess the binding affinity between ligands and receptors, and selected key genes were further validated through cell experiments.

Results

A total of 4062 differentially expressed genes (DEGs) were identified from the GSE35959 dataset. Among these, 58 genes were found to overlap with the targets of prunetin, indicating their potential as therapeutic targets. The enrichment analysis indicated these targets were mainly enriched in MAPK, FoxO, and mTOR signaling pathways. The molecular docking analysis demonstrated that prunetin exhibited strong binding activity with the core targets. Furthermore, cell experiments revealed that prunetin effectively reversed the expression levels of ALB, ESR1, PTGS2, and FGFR1 mRNA in MC3T3-E1 cells treated with dexamethasone (DEX).

Conclusion

Our research revealed the multi-pathway and multi-target features of prunetin in treating OP, shedding light on the potential mechanisms underlying the effectiveness of prunetin against OP. These findings serve as a theoretical foundation for future drug development in this field.

Keywords:

• Osteoporosis
• network pharmacology
• prunetin
• molecular docking
• bioinformatics analysis

Author contributions

Jing Wu wrote the main manuscript text. Jiali Chen and Xijing Yu prepared figures and performed molecular docking analysis. Yujuan You edited the article. All authors reviewed the manuscript.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University.

Disclosure statement

All authors declared that they have no competing interests.

Data availability statement

All data are available from the corresponding author upon request.

Additional information

Funding

This work was supported by the Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine (No. 2022A160) and Science and Technology Plan of Jiangxi Provincial Health Commission (No. 202311319).