Targeted suppression of cytokine-mediated inflammation in rheumatoid arthritis by Melia azedarach L. extract

Inflammation is a critical contributor to the pathogenesis of rheumatoid arthritis (RA), primarily mediated by NF-κB signalling. Medicinal plants have long been utilised for the treatment of inflammatory disorders, including RA, due to their minimal side effects and cost effectiveness. The current study was designed to explore the anti-inflammatory potential of Melia azedarach L. and to validate its traditional use in rheumatic disorders. Ethanolic extract of Melia azedarach (Ma.EE) was prepared and characterized by GCMS and FTIR techniques. Phytochemicals presents in the Ma.EE were quantified and extract was screened for free radical scavenging potential in in vitro antioxidant assays (DPPH and CUPRAC). Different doses Ma.EE (100, 200 and 400 mg/kg) were tested in acute inflammatory (carrageenan, serotonin and histamine-induced paw oedema) and CFA-induced arthritic models. qPCR analysis were performed to investigate the potential underlying mechanisms of inflammation reduction. GC-MS analysis confirmed the presence of anti-inflammatory compounds including oleic and erucic acid in Ma.EE and quantitative assays revealed high flavonoid (236.20 ± 12.09 mg QE/g DE), phenolic (34.66 ± 1.56 mg GAE/g DE), tannin (79.86 ± 26.73 mg TAE/g DE), and saponin (27.2%) contents. In vivo studies showed that Ma.EE (100, 200, 400 mg/kg) significantly (p < 0.001) attenuated paw oedema, particularly at 200 and 400 mg/kg. In the chronic model of paw inflammation, sustained reduction in paw volume was observed along with down-regulated (p < 0.001) mRNA expression of NF-κB, TNF-α, IL-1β, COX-2, and up-regulation of IL-10 respectively. Biochemical assessments showed decreased ALT and AST levels, while radiographic and histopathological analyses confirmed reduced joint damage and neutrophil infiltration. These findings suggest that Ma.EE exerts potent anti-inflammatory effects by modulating the NF-κB and COX-2 regulated cellular and molecular interactions.