Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway
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En-Xing Xue1,*, Jian-Ping Lin2,*, Yu Zhang1, Sun-Ren Sheng1, Hai-Xiao Liu1, Yu-Long Zhou1 and Hui Xu1
1Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
2Department of Orthopedic Surgery, Hainan Provincial People's Hospital, Haikou, Hainan, 570311, China
*These authors contributed equally to this work
Hui Xu, email: email@example.com
Keywords: pterostilbene, nuclear factor erythroid 2-related factor 2, chondrocyte, inflammation, reactive oxygen species
Received: December 08, 2016 Accepted: March 09, 2017 Published: March 30, 2017
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.
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