Therapeutic and Protective Efficacy of Esculetin on Inflammation and Cartilage Injury by Monosodium Iodoacetate‑Induced Osteoarthritis in a Sprague‑Dawley Rat Model

Background: Osteoarthritis (OA) is a major bone‑related disease, which is characterized by joint deterioration, bone destruction, and whole joint damage, leading to permanent disability. The present study aimed to assess the anti‑inflammatory and anti‑osteoarthritic effects of esculetin in a monosodium iodoacetate (MI)‑induced OA model in Sprague‑Dawley (SD) rats. Materials and Methods: The anti‑osteoarthritic efficacy of esculetin was determined in an MI‑induced OA animal model. Rats were divided into the following groups: group I: normal control (saline), group II (MI only treated), group III (MI + esculetin), and group IV (MI + indomethacin). The potent outcome of esculetin treatment was assessed through its effects on the proinflammatory cytokines’ levels, weight‑bearing distribution, and histopathologic observation. Anti‑inflammation efficacy of esculetin was evaluated in lipopolysaccharide (LPS)‑induced Ralph and William’s cell line 264.7 (RAW 264.7) cells. Results: In vitro results showed that esculetin has an anti‑inflammatory efficacy through lessening the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor‑alpha (TNF‑α), interleukin (IL)‑1β, and IL‑6 in LPS‑induced RAW cells. Furthermore, esculetin also reinforced the retrieval of hind limb weight‑holding capacity, downregulated the generation of inflammatory mediators and proinflammatory cytokines, and shielded or protected the cartilage tissue from damage in the OA model SD rats. Conclusion: Esculetin seems to be a beneficial therapeutic compound for handling OA and OA‑based disease conditions.