8-Methoxypsoralen has Anti-inflammatory and Antioxidant Roles in Osteoarthritis Through SIRT1/NF-κB Pathway

被引:19
作者
Li, Jichao [1 ]
Zhang, Zeng [2 ]
Qiu, Jinan [1 ]
Huang, Xiaohan [1 ]
机构
[1] Luoyang Orthoped Hosp Henan Prov, Orthoped Hosp Henan Prov, Dept Knee Injury 3, Luoyang, Peoples R China
[2] Zhengzhou Orthoped Hosp, Zhengzhou, Peoples R China
关键词
osteoarthritis; 8-methoxypsoralen; inflammation; oxidative stress; SIRT1; NF-KAPPA-B; PAPAIN-INDUCED OSTEOARTHRITIS; PROTECTS CHONDROCYTES; SIRT1; INFLAMMATION; EXPRESSION; APOPTOSIS; DIAGNOSIS; CELLS;
D O I
10.3389/fphar.2021.692424
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Osteoarthritis (OA) is mainly manifested by joint pain, stiffness and mobility disorder, which is the main cause of pain and disability in middle-aged and elderly people. In this study, we aimed to explore the role and mechanism of 8-Methoxypsoralen (8-MOP) in the OA model both in vitro and in vivo. The rat chondrocytes were treated with IL-1 beta, and the proliferation, apoptosis, inflammatory reactions and oxidative stress responses were determined after treatment with different concentrations of 8-MOP. Real-time quantitative polymerase chain reaction (qRT-PCR) and/or Western blot were implemented to check the AMPK/SIRT1/NF-kappa B expression in chondrocytes. The NF-kappa B activity was determined by dual luciferase experiment. The pain threshold of OA rat model dealt with 8-MOP and/or the SIRT1 inhibitor EX527 was measured. Our results revealed that 8-MOP evidently reduced IL-1 beta-mediated apoptosis and inhibition of proliferation, and mitigated the expression of inflammatory cytokines and oxidative stress factors in chondrocytes. Additionally, 8-MOP promoted phosphorylated level of AMPK alpha, enhanced SIRT1 expression and inhibited the phosphorylation of NF-kappa B. After treatment with EX527, 8-MOP-mediated protective effects on chondrocytes were mostly reversed. In vivo, 8-MOP obviously improved the pain threshold in the OA rat model and reduced the injury and apoptosis of chondrocytes in the joints. In addition, 8-MOP relieved inflammatory and oxidative stress responses in the articular cartilage via enhancing SIRT1 and repressing NF-kappa B activation. After the treatment with EX527, the 8-MOP-mediated protective effects were distinctly weakened. In summary, our study testified that 8-MOP alleviates pain, inflammatory and oxidative stress responses in OA rats through the SIRT1/NF-kappa B pathway, which is expected to become a new reagent for clinical treatment of OA.
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页数:15
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