Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling.
Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling.
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Gedunin 通过激活 Nrf2/ARE 信号传导对抗类风湿关节炎的重要性
DOI：
10.1155/2022/6277760
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发表时间：
2022
影响因子：
--
通讯作者：
Huang, Ming-Qing
中科院分区：
文献类型：
--
作者：
Chen, Jian-Yu;Tian, Xiao-Yun;Liu, Wen-Jing;Wu, Bao-Kun;Wu, Yue-Chan;Zhu, Ming-Xing;Jin-Liu;Zhou, Xian;Zheng, Yan-Fang;Ma, Xue-Qin;Huang, Ming-Qing
本研究评价葛豆宁(Gedunin，GDN)对关节组织的抗炎和保护作用，揭示其抑制类风湿关节炎(RA)的可能机制。采用脂多糖诱导的巨噬细胞、肿瘤坏死因子-α刺激的滑膜成纤维细胞或IL-1β刺激的原代类风湿关节炎滑膜成纤维细胞，观察其抗炎作用。此外，我们还采用CIA诱导的关节炎模型来评价其抗炎作用。采用四甲基偶氮唑盐比色法和四甲基偶氮唑蓝比色法检测细胞活性和增殖活性，Q-聚合酶链式反应检测细胞因子的mRNA表达，流式细胞仪检测细胞内ROS的产生，Western blotting和siRNA干扰实验证实GDN通过Nrf2信号转导途径发挥抗关节炎作用。结果。在体外，巨噬细胞和MH7A细胞的细胞活力受到抑制，而RASF则不受抑制；但RASF的增殖受到显著抑制，并呈时间和剂量依赖关系。GDN抑制脂多糖刺激的巨噬细胞和肿瘤坏死因子-α刺激的MH7A细胞或RASF中的细胞因子水平。GDN抑制ROS的表达。此外，GDN可剂量依赖性地降低脂多糖诱导的巨噬细胞iNOSmRNA和蛋白的表达。SiP62干扰结果显示，siP62干扰后，GDN导致HO-1和Keap1表达减少，也不能抑制细胞因子的表达。在体内，GDN有效地抑制了足肿胀、关节炎评分、关节炎发生率和细胞因子。我们的研究表明，GDN在体外和体内都通过激活Nrf2信号通路对关节炎有很强的拮抗作用。我们的工作将为类风湿关节炎的治疗提供一个有前景的策略。
This study assessed the anti-arthritic effect and protection of Gedunin (GDN) on joint tissues and revealed the possible mechanism in suppressing rheumatoid arthritis (RA). LPS-induced macrophages and TNF-α-stimulated synovial fibroblasts (MH7A) or IL-1β-stimulated primary rheumatoid arthritis synovial fibroblasts (RASFs) were used to evaluate the antiinflammatory effect of GDN. In addition, CIA-induced arthritis was employed here to evaluate the anti-arthritic effect. MTT and BRDU assays were utilized to evaluate the cell viability and proliferation, Q-PCR was conducted to detect the mRNA expression of cytokines, FACS was adopted to monitor ROS production, while western blotting (WB) and siRNA interference were applied in confirming the anti-arthritic effects of GDN via the Nrf2 signaling. Results. In vitro, cell viability was inhibited in macrophages and MH7A cells, but not in RASFs; but the proliferation of RASFs was significantly suppressed in time- and dose-dependent manners. GDN suppressed cytokine levels in LPS-stimulated macrophages and TNF-α-stimulated MH7A cells or RASFs. GDN suppressed ROS expression. Furthermore, GDN treatment notably dose-dependently decreased the mRNA and protein expression of iNOS in LPS-induced macrophages. sip62 interference results showed that GDN cause the less expression of HO-1 and Keap1 and also fail to inhibit cytokines after sip62 interference. In vivo, GDN effectively inhibited paw swelling, arthritis score, and arthritis incidence and cytokines. Our study suggested that GDN exhibited strong antagonistic effect on arthritis both in vitro and in vivo via activation of Nrf2 signaling. Our work will provide a promising therapeutic strategy for RA.
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DOI：
10.3390/molecules20022636
发表时间：
2015-02-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Conte FP;Ferraris FK;Costa TE;Pacheco P;Seito LN;Verri WA Jr;Cunha FQ;Penido C;Henriques MG
通讯作者：
Henriques MG
影响因子：
7.4
作者：
Reuter, Simone;Gupta, Subash C.;Chaturvedi, Madan M.;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
27.4
作者：
Wruck, Christoph Jan;Fragoulis, Athanassios;Pufe, Thomas
通讯作者：
Pufe, Thomas
影响因子：
7.3
作者：
Lee, AK;Sung, SH;Kim, SG
通讯作者：
Kim, SG
影响因子：
16.6
作者：
Kobayashi EH;Suzuki T;Funayama R;Nagashima T;Hayashi M;Sekine H;Tanaka N;Moriguchi T;Motohashi H;Nakayama K;Yamamoto M
通讯作者：
Yamamoto M