Alaa Elmetwalli, Ashraf Elsayed, Samaa Ahmed El-Sakka, Ghadeer H Albalawi, Faisal H Altemani, Ahmed E Noreldin, Dalia Wael, Zeinab A Ali, Rabab A Mohamed, Mervat G Hassan
Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive cartilage degradation, chronic inflammation, and joint structural deterioration. Beyond its physical burden, OA significantly impacts psychological well-being and socioeconomic stability. Current pharmacological treatments, such as meloxicam (Mel), provide symptomatic relief but fail to comprehensively address the inflammatory mechanisms driving OA progression while also posing risks like liver toxicity. The study was designed to test whether exopolysaccharide (EPS) improves cartilage structural integrity in a ciprofloxacin (CIP)-induced OA-like experimental arthropathy, with inflammatory, oxidative, and signaling markers serving as supportive mechanistic outcomes. The EPS-producing Bacillus altitudinis strain BAE2023 was identified via 16S rRNA sequencing, with EPS composition confirmed through GC/MS and FTIR analyses. Forty male albino rats were divided into five groups: control, CIP-induced OA-like experimental arthropathy, and treatment groups receiving EPS, Mel, or their combination. Results demonstrated that combined EPS and Mel therapy significantly improved joint structural parameters, improved the measured redox profile by increasing SOD, GST, and GSH and by lowering MDA, a marker of lipid peroxidation, and suppressed key circulating inflammatory mediators. Gene expression analysis revealed that EPS successfully modulated the Nrf2/Ho-1 and Cox-2/Mmp1a signaling axes, highlighting its role in inflammation resolution and joint repair. Histopathological evaluation further confirmed cartilage regeneration and reduced hepatic toxicity. By effectively modulating inflammation and oxidative stress, EPS emerges as a promising therapeutic strategy for managing disability-related OA. This study underscores the potential of EPS in enhancing joint health, minimizing medication-induced toxicity, and improving overall quality of life for individuals suffering from OA. Integrating EPS into OA treatment paradigms may offer a more holistic, a chondroprotective and structure-preserving effect to disability management.