Immunomodulatory and Antioxidant Potencies of γ-irradiated Piper cubeba in Complete Freund's Adjuvant-Induced Arthritis in Rats.

Piper cubeba (P. cubeba), renowned for its antioxidant properties, has traditionally been used to counteract pro-oxidant effects caused by toxicants. This study investigated the potential immunomodulatory and antioxidant activities of γ-irradiated P. cubeba in a model of rheumatoid arthritis (RA) induced by complete Freund's adjuvant (CFA) in female Wistar rats. RA was induced by a single subcutaneous injection of 0.1 mL of CFA into the right hind footpad. For 3 weeks, arthritic rats received an oral dose of methanolic extract of γ-irradiated P. cubeba (50 mg/kg body weight/day). Blood and tissue samples were measured for MMP-1, MMP-3, ACCP, TNF-α, IL-17, IL-10, and NQO1 levels using ELISA, as well as for the oxidative stress marker MDA and the antioxidant enzyme SOD. CFA-induced RA resulted in marked increases in the expression of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha, oxidative stress markers, and matrix metalloproteinases. Meanwhile, treatment with irradiated P. cubeba reduced the severity of these changes by increasing anti-inflammatory cytokine IL-10 and enhancing FOXP3 expression, a key regulator of T regulatory (Treg) cells, in arthritic rats. These findings demonstrate that irradiated P. cubeba exerts immunomodulatory, antioxidant, and anti-inflammatory effects.