Lycium barbarum polysaccharides exert an antioxidative effect on rat chondrocytes by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway

Introduction: Oxidative stress is the main cause of osteoarthritis (OA). Lycium barbarum polysaccharides (LBP) have antioxidant properties. Thus, the potential effect of LBP on H₂O₂-stimulated chondrocytes was examined.

Material and methods: The cell viability was detected by CCK-8. The reactive oxygen species (ROS) production and apoptosis rates were determined by flow cytometric analysis. The DNA damage was detected by comet assay. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to examine the expression of histone 2A family member X (γH2AX), checkpoint kinase 1 (Chk1), poly ADP-ribose polymerase (PARP), cysteinyl aspartate specific proteinase (caspase)-3/8/9, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its antioxidant-response element (ARE) dependent factors including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1).

Results: Compared to the H₂O₂ group, LBP inhibited the ROS production and DNA damage caused by H₂O₂ (p < 0.05), respectively. LBP inhibited the mRNA and protein expressions of γH2AX and Chk1 (p < 0.05). Meanwhile, LBP significantly decreased apoptosis (p < 0.05). And LBP inhibited the expression levels of PARP and Caspase-3/8/9 (p < 0.05). Moreover, LBP increased the expression of Nrf2, HO-1and NQO-1 (p < 0.05). Furthermore, the depletion of Nrf2 that mediated by RNA interference reversed the apoptosis and DNA damage inhibition effect of LBP (p < 0.05).

Conclusions: LBP protected chondrocytes through inhibiting DNA damage and apoptosis caused by H₂O₂, in which the Nrf2/ARE signaling pathway played a positive role. It provided an inspiration for clinical application - developing LBP as a therapeutic agent and Nrf2 as a promising candidate.

Keywords: Lycium barbarum polysaccharides; antioxidant; nuclear factor (erythroid-derived 2)-like 2 (Nrf2); osteoarthritis.