AccScience Publishing / EJMO / Volume 9 / Issue 2 / DOI: 10.36922/EJMO025150103
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ORIGINAL RESEARCH ARTICLE

Network pharmacology and bioinformatics reveal the multi-target mechanisms of the Qiang-gu-jian-shen formula osteoporosis treatment

Cuicui Zhou1,2 ,  Zarina Awang1 ,  Farra Aidah Jumuddin1*
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1 Department of Clinical Medicine, Faculty of Medicine, Lincoln University College, Petaling Jaya, Selangor, Malaysia
2 Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanyang Medical College, Nanyang, Henan, China
EJMO 2025, 9(2), 268–282; https://doi.org/10.36922/EJMO025150103
Received: 10 April 2025 | Revised: 13 May 2025 | Accepted: 14 May 2025 | Published online: 18 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and deteriorated bone microstructure, significantly increasing fracture risk. As global aging intensifies, OP has become a significant public health issue. Present pharmacological interventions, such as bisphosphonates and selective estrogen receptor modulators, are associated with side effects and limitations, highlighting the need for safe and effective alternatives. Objective: This study investigates the potential mechanisms of the Qiang-gu-jian-shen formula (QGJSF), a traditional Chinese medicine (TCM) compound, in treating OP using network pharmacology and bioinformatics. Methods: A total of 1,395 potential targets for QGJSF were identified by querying the TCMSP and BATMAN-TCM databases and converting targets through UniProt. Cross-referencing with OP-related targets from GeneCards, OMIM, and DisGeNET yielded 500 mapped targets. Protein-protein interaction network constructed through the STRING database led to the identification of 69 core targets. An “herb-active component-target” network was built using Cytoscape 3.9.0. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses highlighted key pathways, including the PI3K/AKT and FoxO. Results: Molecular docking showed that key components, such as quercetin, dioscin, genistein, calycosin, and berberine, bind favorably to core targets (binding energies < −5 kcal/mol). GEO dataset (GSE5958) analysis identified seven common core genes, including TGFB1, MMP2, BCL2L1, MAPK3, AKT1, CTNNB1, and TP53. The findings suggest that QGJSF may improve OP through multiple components that regulate osteoblast differentiation, osteoclastogenesis, and activate key pathways, such as Wnt/β-catenin, PI3K/AKT, and JAK/STAT, thereby enhancing bone formation and reducing resorption. Core targets such as ESR1, STAT3, AKT1, and TP53 regulate bone metabolism by modulating osteoblasts, osteoclasts, and their interactions with immune and hematopoietic cells to maintain bone remodeling. Conclusion: This study advances understanding of QGJSF’s mechanisms and provides a foundation for novel OP therapies. Future validation and exploration of additional therapeutic targets and mechanisms are needed.

Graphical abstract
Keywords
Qiang-gu-jian-shen formula
Osteoporosis
Network pharmacology
Mechanisms
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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