Biochemical investigations, in silico study and targeted delivery aspects of plant phytosterols: β-sitosterol

Rheumatoid arthritis (RA) is an autoimmune disorder marked by persistent joint inflammation, cartilage deterioration, and systemic effects. Conventional treatment regimens, including biologics and non-steroidal anti-inflammatory drugs (NSAIDs), are often accompanied by significant drawbacks, underscoring the need for novel therapeutic strategies. Among plant-derived bioactives, phytosterols have gained attention for their immunomodulatory and anti-inflammatory properties, with beta-Sitosterol (β-SS) standing out as a potent candidate for RA management. This review provides a comprehensive overview of β-sitosterol (β-SS), highlighting its biochemical properties, therapeutic significance, and mechanisms of action in rheumatoid arthritis (RA). β-SS modulates inflammatory signaling pathways by downregulating pro-inflammatory cytokines, including tumor necrosis factors and interleukins, while simultaneously attenuating oxidative stress. Through these actions, β-SS helps preserve cartilage integrity and supports bone health. Computational studies, including molecular docking and molecular dynamics simulations, have validated its interaction with RA-associated targets, suggesting its potential role in disease modulation. Advances in nanocarrier-based drug delivery systems, including polymeric nanoparticles, liposomes, and micelles, have shown promise in enhancing β-SS stability, controlled release and targeted accumulation in inflamed synovial tissues. Additionally, the review highlights regulatory considerations, technological innovations, and future research avenues to optimize β-SS-based RA interventions. With the integration of computational modeling and modern formulation strategies, β-SS presents a compelling natural alternative for improving RA therapeutics.