Juglanin Attenuated Adjuvant‑Induced Arthritis via Inactivating NF‑κB/IκBα and A Disintegrin‑Like and Metalloproteinase Domain with Thrombospondin‑1 Repeat Pathways in Experimental Rats

Objective: The present study was undertaken to evaluate their possible mechanism of action against adjuvant‑induced arthritis (AIA), i.e., Freund’s complete adjuvant (FCA)‑induced arthritis, in experimental rats. Materials and Methods: FCA (0.1 mL) was administered into the subplantar region of female Wistar rats paw to induced AIA. The rats were treated with vehicle (distilled water, 10 mL/kg) or leflunomide (10 mg/kg), or juglanin (10, 20, and 40 mg/kg, respectively) orally for the next 16 days. Various biochemical, molecular, and histological parameters were evaluated to determine the potential of juglanin. Results: Subplantar administration of FCA resulted in a statistically significant (P < 0.05) induction of AIA reflected by alteration in paw volume, joint diameter, paw withdrawal threshold, and paw withdrawal latency, which was statistically significantly inhibited (P < 0.05) by juglanin (20 and 40 mg/kg). It also statistically significantly attenuated (P < 0.05) FCA‑induced elevated hepatic oxido‑nitrosative stress and mRNA expressions of tumor necrosis factor‑alpha (TNF‑α), interleukin (IL) IL‑1β, IL‑6, transforming growth factor‑beta (TGF‑β), cyclooxygenase‑2 (COX‑2), and inducible nitric oxide synthase (iNOs). Western blot analysis revealed that juglanin statistically significantly downregulated (P < 0.05) protein expressions of NF‑κB, IκBα, a disintegrin‑like and metalloproteinase domain with thrombospondin‑1 repeats (ADAMTS)‑4, and ADAMTS‑5 in hepatic tissue. It also statistically significantly attenuated (P < 0.05) histopathological anomalies induced in the tibiotarsal joint. Conclusion: The present communication suggests that juglanin attenuated altered mechano‑tactile allodynia and hyperalgesia via inhibition of elevated oxido‑nitrosative stress, cytokines (TNF‑α and ILs) levels, immune‑inflammatory (TGF‑β, NF‑κB, Ikβα, COX‑2, and iNOs) mediators, and ADAMTS, thus exerting its anti‑arthritic potential.