Therapeutic effect and molecular associated mechanisms of silymarin on osteoarthritis: A systematic review

Background and aims: Osteoarthritis (OA) is a degenerative joint and common skeletal disease around the world. We aimed to review silymarin and its major active constituent effects and underlying mechanisms for relieving OA. Methods: The study protocol was designed according to the PRISMA statement. An extensive search was performed in several main databases including PubMed, Web of Science, EMBASE, and Scopus. Considering the inclusion and exclusion criteria of the study, finally, ۱۱ studies were included. The desired data were extracted from the studies and registered into an Excel form and the consequences and mechanisms were surveyed. Results: Silymarin, inhibits or downregulates IL (interleukin)-۱β, IL-۶, IL-۸, IL-۱۷, tumour necrosis factor alpha (TNF-α), prostaglandin E۲ (PGE۲), matrix metalloproteinase (MMP)-۱, MMP-۳, MMP-۱۳, inducible nitric oxide synthase (iONS), cyclooxygenase-۲ (COX-۲), and high-sensitivity C-reactive protein (hs-CRP). In terms of antioxidant capacity, it decreased reactive oxygen species (ROS), malondialdehyde (MDA), and lipid peroxidation in serum and synovial fluid. In addition, it reduced alkaline phosphatase (ALP), leukocytes (Th۱۷), and HB levels. Silymarin increases superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx). Moreover, it can up-regulate and increases the anabolism of sirtuin۱ (Sirt۱), SRY-box transcription factor ۹ (SOX۹), IL-۱۰, IL-۴, tissue inhibitor of metalloproteinase (TIMP-۱), Collagen type II and extracellular matrix (ECM) homeostasis. Conclusion: Because silymarin is a potent anti-inflammatory and antioxidant polyphenolic flavonoid, it can be effectively used as adjunctive therapy in the treatment of OA; however, more clinical trial studies are still needed to determine its side and analgesic effects.