Page 288 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology QGJSF multi-target mechanisms in osteoporosis

supports the hypothesis that QGJSF exerts its anti-OP regulatory thresholds, while the bidirectional effects of
effects predominantly through stabilizing PI3K/AKT pathways such as PI3K/AKT may depend on component
signaling (via AKT1 activation) and mitigating TP53- concentrations and microenvironmental factors,
driven osteoblast apoptosis. necessitating quantification using 3D bone organoids or
These findings collectively highlight a “multi- dynamic culture systems. Future studies could integrate
component, dual-core target” mechanism: QGJSF’s active spatial transcriptomics and single-cell metabolomics
ingredients physically engage AKT1 and TP53 to rectify to elucidate the spatiotemporal regulatory network of
their dysregulation in OP, while other targets (e.g., STAT3, QGJSF in bone vascularization and oxidative stress
CTNNB1) may contribute indirectly through pathway microenvironments. In addition, combining clinical
crosstalk or compensatory mechanisms. Future studies heterogeneity data to establish efficacy prediction models
should prioritize in vitro validation of these docking will advance precision intervention strategies for OP
interactions, for example by testing whether quercetin treatment using TCM formulations.
or dioscin modulates AKT1 phosphorylation or TP53 Acknowledgments
activity, to strengthen the translational relevance of these
computational insights. None.

5. Conclusion Funding
QGJSF potentially treats OP by acting through its None.
components, quercetin, dioscin, genistein, calycosin,
and berberine, on potential core targets such as STAT3, Conflict of interest
AKT1, TP53, ESR1, and JUN. These interactions modulate The authors declare they have no competing interests.
several signaling pathways including PI3K/AKT, FoxO,
HIF-1, cellular senescence, and osteoclast differentiation. Author contributions
The formula intervenes in BP such as positive regulation Conceptualization: Farra Aidah Jumuddin
of gene expression, RNA polymerase II transcription, cell Formal analysis: Zarina Awang
proliferation, as well as negative regulation of apoptosis Investigation: Cuicui Zhou
and cell proliferation. These molecular insights provide a Methodology: Cuicui Zhou, Farra Aidah Jumuddin
theoretical basis for subsequent clinical and experimental Writing – original draft: Cuicui Zhou
studies on OP treatment. However, it is important to Writing – review & editing: Cuicui Zhou, Zarina Awang
acknowledge the limitations of this study. The present
analysis focuses solely on the direct relationships between Ethics approval and consent to participate
QGJSF and OP-related components, targets, and pathways.
Given that QGJSF is a TCM compound prescription, it Not applicable.
may also improve the overall condition of OP patients by Consent for publication
indirectly addressing pathological changes across multiple
systems. This potential indirect therapeutic mechanism Not applicable.
remains to be explored and elucidated further. The above
findings provide valuable guidance for future research Availability of data
directions. Investigating the indirect effects of QGJSF Not applicable.
on systemic health could offer additional strategies for
treating OP and enhancing the quality of life for affected References
individuals. Moreover, understanding the comprehensive 1. International Osteoporosis Foundation. Worldwide
mechanisms of QGJSF will contribute to the development Incidence of HIP Fracture Increase from 1990 to 2050 [EB/
of more effective and personalized therapies for OP. OL]. Available from: https//www.osteoporosisfoundation/
This study reveals potential molecular mechanisms by policy-makers#policy-reports-audits [Last accessed on 2025
which QGJSF regulates bone metabolism through multi- Jun 16].
dimensional analyses. Nonetheless, the synergistic effects 2. World Health Organization. Musculoskeletal Conditions
of its components and dynamic regulatory mechanisms Affect Millions [EB/OL]. Available from: https://www.who.
require further exploration. For instance, functional int/news/item/27-10-2003musculoskeletal-conditions-
validation of core targets (e.g., AKT1, TP53) requires affect-millions [Last accessed on 2025 Jun 16].
validation through gene-editing models to define their 3. Schroeder RJ, Staszkiewicz J, O’Quin C, et al. Oral

Volume 9 Issue 2 (2025) 280 doi: 10.36922/EJMO025150103