EXPLORING BIOCHEMICAL PATHWAYS IN RHEUMATOID ARTHRITIS: INSIGHTS INTO ANTI-INFLAMMATORY ROLES OF TRACE ELEMENTS AND URSOLIC ACID
Main Article Content
Keywords
Rheumatoid arthritis, Biochemical pathways, Anti-inflammatory therapy
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease involving complex pathways driven by cytokine dysregulation and oxidative stress. This article investigates the role of trace elements such as copper (Cu), selenium (Se), and zinc (Zn) in the treatment of RA and their biochemical pathways about ursolic acid (UA). Experiments performed in a mouse model of arthritis show that UA when combined with metal complexes, improves therapeutic cytokine protection while inhibiting inflammatory cells such as NF-A, TLR-4, and TNF-alpha. Molecular interactions in this biochemical process have been shown to have two roles: inhibiting inflammation and promoting tissue repair. Additionally, UA complexes have negligible toxicity and have been suggested for use as alternative therapies or treatments such as nonsteroidal anti-inflammatory drugs. This information provides a way to use natural and therapeutic interventions to target the effects of RA and improve patient outcomes.
References
1. Abdollahi, M., Rahmat, A., & Tashakor, G. (2014). Antioxidant, anti-inflammatory, and immunomodulatory effects of ursolic acid: A review. Food Science and Biotechnology, 23(5), 1207–1215. https://doi.org/10.1007/s10068-014-0168-y
2. Ahmed, S., Anuntiyo, J., Malemud, C. J., & Haqqi, T. M. (2005). Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: A review. Evidence-Based Complementary and Alternative Medicine, 2(3), 301–308. https://doi.org/10.1093/ecam/neh117.
3. Arend, W. P. (2001). The mode of action of cytokine inhibitors in the treatment of rheumatoid arthritis. Arthritis & Rheumatism, 45(1), 101–106. https://doi.org/10.1002/1529-0131(200102)45:1<101::aid-anr14>3.0.co;2-h
4. Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860– 867. https://doi.org/10.1038/nature01322
5. Dinarello, C. A. (2000). Proinflammatory cytokines. Chest, 118(2), 503–508. https://doi.org/10.1378/chest.118.2.503
6. Heo, H. J., & Kim, D. O. (2004). Ursolic acid protects neuronal cells from oxidative stress and brain ischemia via the Nrf2 pathway. Journal of Agricultural and Food Chemistry, 52(24), 7287–7291. https://doi.org/10.1021/jf049124u
7. Kanazawa, T., Tsubota, A., & Matsuyama, T. (2020). Trace elements and oxidative stress in inflammatory conditions. Clinica Chimica Acta, 508, 7–11. https://doi.org/10.1016/j.cca.2020.05.002
8. Makarov, S. S. (2001). NF-kappaB as a therapeutic target in chronic inflammation: Recent advances. Molecular Medicine Today, 6(11), 441–448. https://doi.org/10.1016/s1357- 4310(00)01888-3
9. Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011). The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1813(5), 878–888. https://doi.org/10.1016/j.bbamcr.2011.01.034
10. Zhao, W., Zhao, T., Chen, Y., & Ahokas, R. A. (2015). Ursolic acid reduces pro-inflammatory cytokine production in rheumatoid arthritis by modulating TLR signaling. Journal of Immunology, 194(5), 2303–2310. https://doi.org/10.4049/jimmunol.1402340
11. Bagchi, D., & Preuss, H. G. (2007). Role of nutritional supplements in preventing oxidative stress. Toxicology, 234(3), 289–299. https://doi.org/10.1016/j.tox.2007.01.033
12. Bhattacharya, A., & Rahman, M. M. (2016). Trace elements and their roles in rheumatoid arthritis. Clinical Rheumatology, 35(1), 19–28. https://doi.org/10.1007/s10067-015-3065-
9
13. Cantley, L. C., & Semenza, G. L. (2021). Mechanisms of disease progression in autoimmune arthritis. Cell Metabolism, 33(2), 242–250. https://doi.org/10.1016/j.cmet.2020.12.007
14. Duan, W., Zhang, H., & Lu, X. (2015). Therapeutic potential of trace elements in modulating inflammatory responses. Biological Trace Element Research, 166(2), 87–95. https://doi.org/10.1007/s12011-015-0261-3
15. Hardy, C. J., & Woodward, P. E. (2002). Oxidative stress in rheumatoid arthritis: Pathogenic and therapeutic implications. Clinical Immunology, 104(3), 225–232. https://doi.org/10.1006/clim.2002.0224
16. Hossain, M. S., & Yamamoto, H. (2018). Ursolic acid's regulatory role in oxidative stress pathways in autoimmune arthritis. Free Radical Biology and Medicine, 115, 162–172. https://doi.org/10.1016/j.freeradbiomed.2018.06.011.
17. Littlejohn, G. (2020). Rheumatoid arthritis and inflammation: The molecular basis of joint damage. Current Opinion in Rheumatology, 32(1), 16–24. https://doi.org/10.1097/BOR.0000000000000675.
18. Pathak, S. K., Tandon, R., & Verma, R. (2013). Trace elements and cytokine modulation in autoimmune conditions. Inflammation Research, 62(10), 893–899. https://doi.org/10.1007/s00011-013-0650-1.
19. Selmi, C., & Gershwin, M. E. (2009). The role of cytokines and chemokines in autoimmunity. Clinical Reviews in Allergy & Immunology, 36(3), 246–255. https://doi.org/10.1007/s12016-008-8116-3.
20. Vossenaar, E. R., & van Venrooij, W. J. (2004). Citrullinated proteins as targets for autoantibodies in rheumatoid arthritis. Nature Reviews Rheumatology, 3(8), 461–470. https://doi.org/10.1038/nrrheum.2010.123.
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
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Farhana Ayub
Department of Biomedical Sciences, King Faisal University, Al Ahsa, Saudi Arabia
Basic Health Sciences Department, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
Abdul Khaliq Naveed
Basic Health Sciences Department, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
Principal Wah Medical College, Wah Cantonment, Pakistan,
Adnan Jehangir
Department of Biomedical Sciences, King Faisal University, Al Ahsa, Saudi Arabia
Basic Health Sciences Department, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan