Protective effects of harmine on Monosodium Iodoacetate-induced Osteoarthritis in rats: In vitro and in vivo studies

Abstract

BackgroundOsteoarthritis (OA) is a painful and debilitating disease, which is characterized by joint pain, swelling, restricted movement, and joint stiffness. It affects more than millions of people worldwide. ObjectiveIn this current work, we aimed to assess the beneficial roles of harmine on the monosodium iodoacetate (MI)-induced OA in rats. MethodologyThe in vitro studies were carried out in the LPS-induced RAW 264.7 cells and administered with 5 and 10 µM of harmine. In in vivo studies, 2.5 mg of MI diluted in 10 ml of saline (9%) was injected into the knee joints of the experimental rats to induce OA. The 25 and 50 mg/kg of harmine was treated one week before the MI injection and continued for 25 days after induction. The paw volume and arthritis score was measured after the completion of treatments. The levels of inflammatory cytokines, PGE-2, and NO in both RAW 264.7 cells and OA-induced rats using the assay kits. The MDA and antioxidants (GSH, CAT, and SOD) levels were assessed using the assay kits. The knee joint tissues were analyzed by histopathological study. ResultsThe treatment with 5 and 10 µM of harmine effectively decreased the PGE-2 and NO levels in the LPS-exposed RAW 264.7 cells. The status of IL-6 and TNF-α also diminished by the harmine in the LPS-induced RAW 264.7 cells. The paw volume and arthritis score was decreased by the harmine treatment. The levels of PGE-2, IL-6, IL-1β, and TNF-α levels were depleted and IL-10 level was augmented by the harmine treatment in the OA-induced rats. The harmine are also suppressed the MDA and elevated the GSH, SOD, and CAT in the OA-induced rats. Further, the therapeutic roles of harmine also evidenced by the findings of the histopathological analysis. ConclusionThe current research suggests that harmine is effective in attenuating OA in rats and significantly decreasing the OA-related oxidative stress and inflammation responses. The harmine also reduced the inflammatory response in the LPS-induced RAW 264.7 cells, therefore, it may be a talented agent for treating OA.