Immunomodulatory properties of a methanolic extract of Ficus lyrata mitigate inflammation in Complete Freund's Adjuvant-induced arthritis.

Ficus lyrata, renowned for its traditional use in alleviating rheumatic pain and inflammation, was validated for its purported anti-arthritic and antiinflammatory properties using InvivoandInvitromodels. In the in-vivo studies, carrageenan-induced acute oedema and a chronic arthritis induced by complete Freund's adjuvant (CFA) were employed. Oral dosing of methanolic extract from Ficus lyrata (m-FL) was administered at (250,500 and 750 mg/kg) as well as methotrexate at 1 mg/kg, significantly (p < 0.0001) demonstrated a dose dependent decrease in percent oedema/inflammation and notably reduced arthritis development in the CFA model, indicating strong anti-inflammatory effects over time. Further analysis revealed m-FL extract inhibited protein denaturation across all evaluated concentrations(1600,800,400,200,100,50 µg/ml) suggesting potential mechanisms for their anti-inflammatory action. Phytochemical analysis identified flavonoids and phenolic compounds in the extract. Gene expression analysis of m-FL extract treatment group using qPCR showed a significant (p < 0.0001) downregulation of various inflammatory markers (IL1,COX2,IL1β, NFκB, TNF,STAT-3,IL6) with simultaneous upregulation in the expression of antiinflammatory markers (IL4,10). The m-FL extract targets TNF-mediated decrease in interleukins specifically IL-1, IL1β and IL-6. Histopathological assessments and radiographic evaluations conducted subsequently demonstrated a significant decline in joint inflammation, bone erosion, and pannus formation, along with improved bone integrity and reduced inflammation in the m-FL extract-treated groups (p < 0.0001). Although the m-FL extract exhibited relatively stronger antioxidant activity compared to ascorbic acid in-vitro, the primary efficacy lies in the potent immunomodulatory and anti-arthritic effects. The m-FL extract showed potential as an adjunct therapy for managing inflammatory conditions.