Ameliorative Efficacy of Oxypaeoniflorin, a Traditional Chinese Medicine Monomer against Adjuvant‑Induced Arthritic Inflammation and Pain

Objectives: The objective of the study is to evaluate the potential of OPA against Freund complete adjuvant (FCA)‑induced inflammatory pain in experimental arthritic rats. Materials and Methods: FCA was administered in female rats (Wistar strain) to induce polyarthritis, followed by 28 days of oral treatment with either vehicle, leflunomide (10 mg/Kg), or OPA (10, 20, and 40 mg/kg). Various parameters were assessed to determine the effect of OPA on pain and inflammatory pathway. Results: Adjuvant‑induced arthritis (AIA)‑induced elevated paw withdrawal latency and threshold suggested induction of arthritic pain. However, OPA (20 and 40 mg/kg) treatment diminished arthritic pain reflected by amelioration of hyperalgesia and allodynia. In addition, OPA showed an effective inhibition (P < 0.05) in FCA‑induced alterations in alkaline phosphatase, alanine transaminase, aspartate aminotransferase, serum albumin, and C‑reactive protein levels. The AIA‑induced elevated oxido‑nitrosative stress, protein levels of tumor necrosis factor‑α, and interleukins in synovial tissue were effectively reduced (P < 0.05) by OPA. Moreover, OPA effectively downregulated (P < 0.05) enhanced nuclear factor‑kappa beta (NF‑κB), Ikβα, iNOs, and COX‑2 mRNA expressions in synovial tissue. OPA also reduced histopathology alteration induced in the tibiotarsal joint by FCA. Conclusion: OPA exerts its antiarthritic property through inhibition of NF‑κB/IκBα pathway to downregulate the activation of pro‑inflammatory cytokines and inflammatory mediator thus, ameliorated arthritic inflammation and pain.