Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway

Abstract

Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was assessed by CCK-8 test. Immunofluorescence and Western blotting explored the nuclear translocation of Nrf2. Nrf2 expression was silenced by siRNA to evaluate the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally, osteoarthritis model was established by the transection of anterior cruciate ligament and partial medial meniscectomy in rats, and then these rats received pterostilbene 30 mg/kg, daily, p.o. for 8 weeks. Histology and immunohistochemistry were used to assess histopathological change and Nrf2 expression in cartilage. Nuclear translocation of Nrf2 was stimulated by pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX-2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS production induced by IL-1β in chondrocytes, partially reversed by the Nrf2 silencing. Pterostilbene prevented cartilage degeneration and promoted the nuclear translocation of Nrf2 in cartilage. These results suggest that pterostilbene could inhibit the IL-1β-induced inflammation and ROS production in chondrocytes by stimulating the nuclear translocation of Nrf2.

Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway

“…Additionally, previous studies showed that activating Nrf2 could attenuate the activation of NF-κB [34]. Furthermore, a large body of studies showed that many natural herbal compounds could inhibit the inflammatory responses of OA by activating the Nrf2 signaling pathway [35,36]. In the present study, our results showed that the expression of Nrf2 and HO-1 were significantly upregulated by morin.…”

Effect of resveratrol and pterostilbene on aging and longevity

“…Moreover, pterostilbene down‐regulated the secretions of IL‐6, interleukin‐18 (IL‐18), vascular endothelial growth factor (VEGF), NO, matrix metalloproteinase‐2 (MMP‐2), and matrix metalloproteinase‐9 (MMP‐9) all events that may be correlated with the suppression of LPS‐induced NF‐κB p65 nuclear translocation in E11 cells . Furthermore, pterostilbene was found to be a potent Nrf2 activator that contributes to inhibit IL‐1β‐mediated inflammation in chondrocytes, as well as attenuate immune‐mediated death of pancreatic β cells . In vivo , pterostilbene possesses potential anti‐neuroinflammatory effect through significantly repressing LPS‐induced IL‐6 and TNF‐α mRNA expression in rat hippocampus .…”

“…Treatment with pterostilbene markedly ameliorated inflammatory response, as evidenced by the decrease in proinflammatory cytokines (IL‐1β, TNFα, and interferon gamma (IFN‐γ) in streptozotocin (STZ)‐induced diabetic mice . In an osteoarthritis model, pterostilbene has protective effect on cartilage degeneration by modulating IL‐1β‐mediated inflammation via nuclear translocation of Nrf2 . Pterostilbene improves the survival rate and alleviate polymicrobial sepsis‐induced liver injury in mice is because of suppressed inflammatory response possibly associated with SIRT1 signaling activation .…”

“…In human keratinocytes, pterostilbene protects against UVB‐induced photo‐damage through phosphatidylinositol‐3‐kinase (PI3K)‐dependent activation of Nrf2/antioxidant response element (ARE) pathway . Pterostilbene suppress the IL‐1β‐induced inflammation and ROS production in chondrocytes by inducing the nuclear translocation of Nrf2 in order to prevent cartilage degeneration . In hippocampal neuronal cells, pterostilbene reduce high glucose‐induced oxidative damage by Nrf2 activation .…”

Potential anti-haematotoxic and antioxidant effects of Pterostilbene against Fluoride: A biochemical, and histomorphogical changes in the erythrocytes of rats

“…PTS on the opposite side rummages NO production in plasma and erythrocyte membrane in NaF-treated rodents because of its antioxidative capacity. PTS prompts the enactment of Nrf2/HO-1 pathway and eNOS phosphorylation in endothelial cells and thus reestablishes the NO level in control condition (Xue et al, 2017).…”