Sodium alginate-encapsulated Colchicum nanoparticles attenuate TNF-α and NF-κB signaling in macrophages: A novel therapeutic strategy for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by macrophage activation and pro-inflammatory signaling, particularly via TNF-alpha and NF-kappa B pathways. Current therapies, including methotrexate and biologic agents, provide clinical benefits but are limited by systemic toxicity, high costs, and treatment resistance. Here, we report the development of sodium alginate (SA)-encapsulated nanoparticles incorporating Colchicum micranthum (CM) and Colchicum chalcedonicum (CC) extracts as a novel therapeutic approach for RA. Phytochemical profiling revealed distinct polyphenolic signatures in CM and CC, with CC exhibiting superior flavonoid content and antioxidant activity. Nanoparticles fabricated via ultrasonic homogenization displayed uniform nanoscale morphology (55-130 nm), enhanced thermal stability, and strong polymer-phenolic interactions, as confirmed by FTIR, DSC, TGA, and FEGSEM analyses. In THP-1 macrophages, free extracts exhibited dose- and time-dependent cytotoxicity, whereas encapsulated forms (SA/CM, SA/CC) improved cell viability and minimized toxicity. Upon LPS stimulation, SA/CC significantly suppressed TNF-alpha and NF-kappa B expression while restoring metabolic activity, outperforming both free extracts and SA/CM. These findings demonstrate that alginate encapsulation not only enhances the safety and bioactivity of Colchicum-derived compounds but also enables targeted modulation of inflammatory pathways central to RA pathogenesis. By combining the anti-inflammatory properties of plant-derived bioactives with the precision of nanodelivery, SA/CC nanoparticles represent a promising, cost-effective alternative to conventional DMARDs and biologics, warranting further preclinical and clinical evaluation.