113-LQP-IJCMR 20260903111243 Lumina Quest Publishing m.arslansohail@gmail.com Lumina Quest Publishing International Journal of Clinical and Medical Research Int. J. Clin. Med. Res. 3134-8831 10.66590/ijcmr https://lquestpub.com/archives.php?journal=international-journal-of-clinical-and-medical-research 06 30 2026 06 30 2026 3 1 10.66590/ijcmr20260301 https://lquestpub.com/articles-list.php?journal=international-journal-of-clinical-and-medical-research&volume=3&issue=1 Nrf2–Keap1 Signaling in Arthritis: Therapeutic Potential of Nanoparticle-Based Approaches with Special Reference to Silver Nanoparticles Muhab Suliman Isra Omar Ali Mukhtar Mahgoub Ahmed Sahoud R. Al-Sultany Mohammed Abdelrazig Ahmed Elrofaie Muhammad Harmain Maqsood Madiha Mahmood Yassir Musa Arthritis represents a heterogeneous group of inflammatory and degenerative joint disorders characterized by persistent inflammation, oxidative stress, cartilage degradation, synovial dysfunction and progressive impairment of joint integrity. Rheumatoid Arthritis (RA) and Osteoarthritis (OA), although distinct in etiology, share several pathological mechanisms involving excessive production of Reactive Oxygen Species (ROS), mitochondrial dysfunction, inflammatory cytokine activation and dysregulation of redox-sensitive signaling pathways [1-4]. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is a major endogenous defense mechanism responsible for maintaining cellular redox homeostasis. Under basal conditions, Keap1 promotes Nrf2 degradation; however, oxidative or electrophilic stress disrupts this interaction, allowing Nrf2 to accumulate and translocate into the nucleus, where it activates antioxidant response element (ARE)-dependent genes, including heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and glutathione-related enzymes [5,6]. Increasing evidence indicates that impaired or insufficient Nrf2 activity contributes to persistent oxidative stress and inflammation in arthritic joints [1,7]. Nrf2 also interacts with major inflammatory pathways, particularly nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and NLRP3 inflammasome signaling [8]. Nanotechnology offers an opportunity to improve the delivery, stability, bioavailability and tissue targeting of therapeutic agents capable of modulating redox and inflammatory pathways. Among different nanomaterials, silver nanoparticles (AgNPs) have attracted considerable interest because of their antimicrobial, anti-inflammatory, antioxidant and immunomodulatory properties [9-11]. Experimental studies have demonstrated that AgNPs can reduce inflammatory cytokines, regulate NF-κB and MAPK signaling, influence macrophage polarization and alleviate inflammatory tissue injury [9,10]. In experimental RA, targeted folic-acid-modified AgNPs have demonstrated the ability to interact with inflammatory macrophages, promote macrophage apoptosis and repolarization and reduce disease severity [12]. Nevertheless, the relationship between AgNP exposure, oxidative signaling and Nrf2-Keap1 activation is complex and excessive nanoparticle-induced oxidative stress may also produce adverse biological effects. This review examines the role of the Nrf2-Keap1 pathway in arthritis, evaluates nanoparticle-based strategies for modulating redox and inflammatory mechanisms and critically discusses the therapeutic potential and safety considerations of AgNPs. Particular emphasis is placed on the potential intersection between AgNP-mediated redox regulation, Nrf2-Keap1 signaling, NF-κB inhibition, macrophage polarization and joint protection. 06 30 2026 06 30 2026 34 39 10.66590/ijcmr2026030105 https://lquestpub.com/article/10.66590/ijcmr2026030105