Medicarpin prevents arthritis in post-menopausal conditions by arresting the expansion of TH17 cells and pro-inflammatory cytokines

Abstract

Autoimmune diseases are characterized by alteration in balance of various cytokines. Rheumatoid arthritis is a well-known inflammatory disease leading to destruction of cartilage at knee and hands. Collagen-induced arthritis (CIA) is a common autoimmune model for rheumatoid arthritis study. Here, we have investigated the therapeutic role of medicarpin, a natural pterocarpan with known anti-osteoclastogenic activities, in postmenopausal polyarthritis model of DBA/1J mice. For this, mice were ovariectomized and CIA was induced in OVx animals with primary immunization. After 21 days, booster dose was injected in Ovariectomy (OVx) mice to develop postmenopausal poly-arthritis mice model. Medicarpin treatment in mice at dose of 10.0 mg/kg/body wt was started after 21 days of primary immunization for one month of time period every day orally. We found that medicarpin prevented alteration of TH-17/Treg ratio in CIA model leading to reduced osteoclastogenesis. Micro Computed Tomography (Micro-CT) analysis demonstrated that medicarpin prevents cartilage erosion in joints and restores loss of trabeculae parameters in distal tibia. Treatment with medicarpin also prevented alteration of various cytokines level by down-regulating various pro-inflammatory cytokines like TNF-α, IL-6 and IL-17A, while up-regulating anti-inflammatory cytokine IL-10 in CIA model of mice. Biological marker of arthritis is cartilage oligomeric matrix protein (COMP). COMP level was up-regulated in CIA induced mice while treatment with medicarpin significantly restored the serum level of COMP compared with untreated groups. Cartilage staining by Safranin-O also indicates that cartilage destruction in joints of CIA mice was prevented by medicarpin treatment. From this study, we can conclude that medicarpin is effective in preventing arthritis in post-menopausal conditions.