One-pot green synthesis, optimization, and characterization of silver nanoparticles from Mitragyna parvifolia: A novel therapeutic strategy for rheumatoid arthritis targeting COX-2 and TNF- α.

Green nanotechnology offers a sustainable approach to rheumatoid arthritis (RA) therapy by enabling targeted modulation of key inflammatory markers, addressing the limitations of conventional treatments. This study explores biogenic approach to RA therapy through the one-pot green synthesis of silver nanoparticles (AgNPs) using Mitragyna parvifolia bark extract. The synthesis of AgNPs was optimized by varying parameters such as reaction temperature, time, AgNO₃ concentration, extract volume, and pH. The fabricated AgNPs were thoroughly analyzed using UV-visible spectroscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, Energy dispersive X-ray analysis, transmission electron microscopy, and X-ray diffraction, confirming their functional group composition, stability, nano-scale size, spherical shape and face-centered cubic structure. In vitro studies revealed that the AgNPs exhibited superior anti-inflammatory activity compared to the crude plant extract, effectively inhibiting protein denaturation and cyclooxygenase-2 (COX-2) enzyme activity. In vivo assessments using Carrageenan-induced paw edema and Complete Freund's Adjuvant-induced arthritis models revealed significant reductions in paw swelling, inflammatory cytokines (TNF-α and IL-6), and hematological markers of inflammation. Histopathological and radiographic analyses confirmed reduced soft tissue swelling and bone erosion in AgNP-treated groups. Network pharmacology and molecular docking studies identified key phytoconstituents of M. parvifolia targeting TNF-α (PDB ID: 2AZ5) and modulating key inflammatory pathway (TNF signaling pathway). The integration of green synthesis with phytomedicine presents a promising, sustainable, and biocompatible approach to RA treatment. Our findings establish M. parvifolia-derived silver nanoparticles as a promising therapeutic strategy for RA treatment, offering a targeted, sustainable, and effective alternative to conventional therapies through their multi-target modulation of inflammatory pathways.