Investigation of the regenerative effects and mechanisms of action of the polyphenolic compounds on redox stress mediated injury in the pathogenesis of osteoarthritis (OA)

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive pain and loss of function elderly patients. Structural, genetic and metabolic factors are involved in the pathogenesis of OA. Unfortunately, there has been no success in treating OA worldwide. OA is included in WHO's list of priority medicine. The increasing evidence of the cartilage damage occured in OA is related with disturbances of redox stress response of chondrocytes. Phytophenolic compounds have become in focus , due to their antioxidant, anti-inflammatory and redox-regulatory effects in recent studies . So we aimed to reorchestrate the OA therapy with phytochemicals via targeting redox pathways involved in early or onset OA. In our study, astandardized patented mulberry extracts (ImmunFLEX®) and their major bioactive components, Quercetin and Deoxynojirimycin, and also Oleuropein were tested on primary chondrocyte cell cultures isolated from knees of the grade 4 OA patients. The effects of agents on oxidative stress (ROS, 4-HNE, Pentosidine, 3-NT) and apoptotic markers (caspase-3, flow cytometry/ annexin V, mitochondrial membrane potential) were investigated. As a result, agents increased mitochondrial membrane potential at different rates and decreased oxidative and apoptotic parameters. Thus, redox stress-mediated early apoptosis was inhibited and the survival rate in cells increased. Our study provides evidences for the crucial role of supplementing polyphenolic agents in OA therapy.