★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★★Open research. Global perspectives.
editor@theamericanjournals.comPublisher Home ↗
Applied Sciences OPEN ACCESS

In Silico Exploration of Natural Compounds and Drug Repurposing Strategies for FOXO3a Modulation in Metabolic and Autoimmune Muscle Disorders

Torsha Das
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow-226028, India
Pragya Singh
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow-226028, India
Enaya Tufail
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow-226028, India
Somali Sanyal
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow-226028, India
DOI Crossref DOI 10.37547/tajas/warm-11
tajas 2026
JOURNAL PUBLICATION MAY
FULL TEXT PP. 101-106
DOWNLOAD PDF

View all articles in this issue ↗

VOLUME —
ISSUE —
YEAR 2026
PAGES 101-106
RESEARCH OVERVIEW

Abstract

Chronic inflammation, oxidative stress, energy-defective intermediates homeostasis has been gradually recognized in their relevant diseases: metabolic disorders and autoimmune muscle disease including myositis. Forkhead box O3a (FOXO3a), an important transcription factor plays important role in regulating essential cellular processes such as stress response, apoptosis, metabolism homeostasis, and muscle protein turnover. Recent advances in computational biology have allowed for high-throughput screening of FOXO3a-targeting molecules in silico. Flavonoids and polyphenols are different subcategories of phytochemicals that gained attraction due to their remarkable antioxidant, anti-inflammatory, and multi-target abilities. At the same time, drug repurposing strategy is a cost-effective approach because it identifies new therapeutic uses for known approved drugs which have an established safety profile. Here, we review FOXO3a in metabolic and autoimmune muscle disease. It also emphasizes the use of in silico methods to screen phytochemicals and repurposed drugs that may target FOXO pathways as novel therapies for future pharmacologic development.

RESEARCH TOPICS

Keywords

FOXO3a Therapeutic targets Myositis In Silico Drug Discovery Drug repurposing Phytochemicals

Downloads

Download data is not yet available.
SOURCES & SCHOLARSHIP

References

  1. Accili, D., & Arden, K. C. (2004). FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 117(4), 421–426. https://doi.org/10.1016/S0092-8674(04)00452-0
  2. Andersson, K. E. (2018). PDE5 inhibitors and nitric oxide–cGMP signaling. Pharmacological Reviews, 70(3), 601–649. https://doi.org/10.1124/pr.117.014928
  3. Babalola, O.O., Bridget, K., Oyubu, G. et al. Integrating phytochemicals and in silico methods for modern drug discovery: a comprehensive review. Discov. Chem. 2, 297 (2025). https://doi.org/10.1007/s44371-025-00373-y
  4. Brunet, A., Bonni, A., Zigmond, M. J., et al. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96(6), 857–868. https://doi.org/10.1016/S0092-8674(00)80595-4
  5. Calnan, D. R., & Brunet, A. (2008). The FoxO code. Oncogene, 27(16), 2276–2288. https://doi.org/10.1038/onc.2008.21
  6. Cheng, Z., Tseng, Y., & White, M. F. (2017). Insulin signaling meets mitochondria in metabolism. Trends in Endocrinology & Metabolism, 21(10), 589–598. https://doi.org/10.1016/j.tem.2010.06.005
  7. Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics and drug-likeness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
  8. Eijkelenboom, A., & Burgering, B. M. T. (2013). FOXOs: signalling integrators for homeostasis maintenance. Nature Reviews Molecular Cell Biology, 14(2), 83–97. https://doi.org/10.1038/nrm3507
  9. Fasano, C., Disciglio, V., Bertora, S., et al. (2019). FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response. Cells, 8(9), 1110. https://doi.org/10.3390/cells8091110
  10. Giordano, D., Biancaniello, C., Argenio, M. A., & Facchiano, A. (2022). Drug Design by Pharmacophore and Virtual Screening Approach. Pharmaceuticals (Basel, Switzerland), 15(5), 646. https://doi.org/10.3390/ph15050646
  11. Greer, E. L., & Brunet, A. (2005). FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene, 24(50), 7410–7425. https://doi.org/10.1038/sj.onc.1209086
  12. Habrowska-Górczyńska, D. E., Kozieł, M. J., Kowalska, K., & Piastowska-Ciesielska, A. W. (2021). FOXO3a and Its Regulators in Prostate Cancer. International Journal of Molecular Sciences, 22(22), 12530. https://doi.org/10.3390/ijms222212530
  13. Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: An overview. The Scientific World Journal, 2013, 162750. https://doi.org/10.1155/2013/162750
  14. Li, Y., Wang, Y., Kim, E., et al. (2016). Bnip3 mediates the hypoxia-induced autophagy and apoptosis in cardiomyocytes. Cell Death & Disease, 7, e2570. https://doi.org/10.1038/cddis.2016.359
  15. Lipinski, C. A., Lombardo, F., Dominy, B. W., et al. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery. Advanced Drug Delivery Reviews, 46(1–3), 3–26. https://doi.org/10.1016/S0169-409X(00)00129-0
  16. Martins, R., Lithgow, G. J., & Link, W. (2016). Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell, 15(2), 196–207. https://doi.org/10.1111/acel.12427
  17. Meng, X. Y., Zhang, H. X., Mezei, M., et al. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer-Aided Drug Design, 7(2), 146–157. https://doi.org/10.2174/157340911795677602
  18. Morris, G. M., Huey, R., Lindstrom, W., et al. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
  19. Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: An overview. Journal of Nutritional Science, 5, e47. https://doi.org/10.1017/jns.2016.41
  20. Pushpakom, S., Iorio, F., Eyers, P. A., et al. (2019). Drug repurposing: Progress, challenges and recommendations. Nature Reviews Drug Discovery, 18, 41–58. https://doi.org/10.1038/nrd.2018.168
  21. Rojas, C., Slusher, B. S., & Navari, R. M. (2010). Palonosetron: Pharmacology and clinical use. Expert Review of Anticancer Therapy, 10(8), 123–135. https://doi.org/10.1586/era.10.10
  22. Sandri, M., Sandri, C., Gilbert, A., et al. (2004). Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1. Cell, 117(3), 399–412. https://doi.org/10.1016/S0092-8674(04)00400-3
  23. Stitt, T. N., Drujan, D., Clarke, B. A., et al. (2004). The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases. Molecular Cell, 14(3), 395–403. https://doi.org/10.1016/S1097-2765(04)00211-4
  24. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
  25. Yang, S. H., Chang, C., & Lian, Z. X. (2019). Polymyositis and dermatomyositis - challenges in diagnosis and management. Journal of translational autoimmunity, 2, 100018. https://doi.org/10.1016/j.jtauto.2019.100018.
  26. Zhao, J., Brault, J. J., Schild, A., et al. (2007). FoxO3 coordinately activates protein degradation pathways in muscle. Cell Metabolism, 6(6), 472–483. https://doi.org/10.1016/j.cmet.2007.11.004
CONTINUE EXPLORING

Most read articles by the same author(s)

Explore other published research by the authors of this article.