Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway

Recent studies have shown that andrographolide (AP) has the potential to be developed as a drug for therapy for osteoarthritis (OA). However, the role of AP in attenuating the progression of OA is still unknown. We hypothesized that its therapeutic effect may be associated with its antioxidant potential. In this study, we investigated the therapeutic effect of AP on chondrocytes injured by H2O2 and the association with the oxidation-related signaling pathways through the detection of cell proliferation, cell viability, the expression of oxidative stress-specific genes (Sod1, Cat, and malonaldehyde [Mda]) and proteins (superoxide dismutase [SOD], catalase [CAT]) after a culture period of 3 and 5 days, respectively. Further exploration of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)messenger RNA and protein was also performed. The results showed that 0.625 mu g/ml and 2.5 mu g/ml of AP decreased oxidative stress injury of chondrocytes by increasing cell proliferation reduced by H2O2 and antioxidant enzyme activity, including SOD and CAT. Inflammation factors, such as matrix metallopeptidase 13 (Mmp13), tissue inhibitor of metalloproteinase 1 (Timp1), and interleukin-6 (Il6), were downregulated in the H2O2 group with AP, demonstrating a decrease in the progression of OA. Pathway analyses identified that the kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response element (Are) pathway is an important mediator in AP therapy on H2O2-induced OA. This study indicates that AP exerts protection effects on oxidative stress via activation of the Keap1-Nrf2-Are pathway in chondrocytes injured by H2O2, which may be promising for the therapy of OA.