Therapeutic potential of Celtis eriocarpa Decne.: in vivo and in vitro antiarthritic effects supported by GC‒MS and qRT‒PCR analysis.

Rheumatoid arthritis is an autoimmune disorder characterized by cartilage destruction, joint inflammation, and systemic complications. Incomplete disease remission, adverse effects, and limited treatment availability underscore the need for novel therapeutic interventions. With this ultimate goal, the aim of the current study was to assess the anti-inflammatory and antiarthritic potential of chloroform and ethanol extracts of Celtis eriocarpa Decne. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of these extracts revealed the presence of diverse bioactive compounds with well-recognized anti-inflammatory and antiarthritic activities, including phytol, neophytadiene, tocopherols, hexadecenoic acid methyl ester, squalene, and 2-tert-butylphenol derivatives. In vitro assays demonstrated significant, dose-dependent inhibition of protein denaturation by these extracts, with the activity of the chloroform fraction comparable to that of the diclofenac sodium standard. In vivo studies in a formaldehyde-induced arthritis rat model revealed significantly reduced paw edema and arthritis scores and improved mobility after oral administration of Celtis eriocarpa chloroform extracts (CE). Radiographic analysis further confirmed joint preservation in a rat model treated with CE. Histopathological assessments indicated marked reductions in synovial hyperplasia, cartilage erosion, and inflammatory cell infiltration, specifically in the high-dose CE groups. Finally, hematological and biochemical evaluations revealed normalization of inflammatory markers, downregulation of the expression levels of key proinflammatory cytokines (TNF-α, IL-6, NF-κB, IL-1β, and COX-2), and upregulation of the expression levels of anti-inflammatory cytokines (IL-4 and IL-10). Collectively, these findings demonstrate that Celtis eriocarpa extracts are enriched in bioactive phytoconstituents and hold substantial potential as therapeutic candidates for the management of rheumatoid arthritis and inflammatory disorders.