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Not AvailableOsteoarthritis (OA) causes articular cartilage destruction, initiating pain and inflammation in the joints, resulting in joint disability. Medications are available to manage these symptoms; however, their effects on the disease progression are limited.Loss of proteoglycans (PGs) was reported to contribute articular cartilage destruction in OA. Therapeutics approaches were previously studied in the animal models of OA. In the present study, we investigated the oral efficacy of four dosages of PGs (25 milligram per kilogram, 50 milligram per kilogram, 100 milligram per kilogram, 200 milligram per kilogram) , isolated from the bramble shark cartilage, in an animal model of OA. Indomethacin was used as a bioequivalent formulation. Primarily, the mass spectrum analysis of the purifed PGs obtained from bramble shark cartilage revealed the presence of two unique peptides including AGWLSDGSVR and LDGNPINLSK, that showed sequence similarity with aggrecan core-protein and epiphycan, respectively. The levels of C-reactive protein and uric acid in the OA rats were reduced when treated with PGs. Histopathology analysis displayed less cartilage erosion and neovascularization in OA rats treated with PGs. The X-ray imaging presented higher bone density with 200 milligram per kilogram dosage of PG treatment in OA rats. The expressions of the inflammatory modulators including TNF-alpha, IL- 1 beta, MMP13, NOS2, IL-10 and COX-2 were found to be moderated with PG treatment. In addition, PG treatment maintained the activities of antioxidant enzymes, including SOD and catalase in the joint tissues with a higher GSH content, in a dose-dependent manner. Taken together, our preliminary findings report the anti-osteoarthritic properties of PGs and recommend to evaluate its efficacy and safety in randomized trials.Not Availabl