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Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-κB signaling pathways.
Phytomedicine ( IF 6.7 ) Pub Date : 2019-08-01 , DOI: 10.1016/j.phymed.2019.153036 Yarigui Bao 1 , Yue-Wen Sun 1 , Jun Ji 1 , Lu Gan 1 , Chun-Feng Zhang 2 , Chong-Zhi Wang 3 , Chun-Su Yuan 3
Phytomedicine ( IF 6.7 ) Pub Date : 2019-08-01 , DOI: 10.1016/j.phymed.2019.153036 Yarigui Bao 1 , Yue-Wen Sun 1 , Jun Ji 1 , Lu Gan 1 , Chun-Feng Zhang 2 , Chong-Zhi Wang 3 , Chun-Su Yuan 3
Affiliation
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BACKGROUND
Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA.
PURPOSE
This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms.
METHODS
The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis.
RESULTS
Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats.
CONCLUSION
Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).
中文翻译：
Genkwanin通过抑制JAK / STAT和NF-κB信号通路来改善大鼠佐剂性关节炎。
背景技术Genkwanin是从传统中草药Daphne genkwa中分离出来的一种黄酮。我们以前的工作证明，从D. genkwa（FFD）中分离出的四种类黄酮（包括genkwanin）可以显着改善大鼠模型的关节炎症状。最近的研究表明，genkwanin表现出抗炎和免疫调节活性，这两者与类风湿关节炎（RA）的病理密切相关。因此，研究Genkwanin的抗RA作用及其机制可能使我们更深入地了解FFD对RA的治疗作用。目的本研究旨在研究Genkwanin对大鼠佐剂诱发的关节炎（AIA）模型的抗类风湿关节炎的活性，并探讨其潜在机制。方法在AIA大鼠模型上，通过测定爪肿胀程度和关节炎指数评分以及关节组织的组织病理学分析，评估Genkwanin的抗类风湿关节炎活性。用ELISA法测定血清细胞因子水平，用Griess法测定血清NO水平。通过蛋白质印迹分析和免疫组化分析确定JAK / STAT和NF-κB信号通路中蛋白质的表达和磷酸化水平。结果Genkwanin显着降低了AIA大鼠的爪肿胀和关节炎指数，还降低了关节组织的炎症和骨破坏。用Genkwanin处理后，血清TNF-α，IL-6和NO的浓度显着降低，而IL-10的浓度显着升高。Genkwanin抑制AIA大鼠滑膜组织中JAK / STAT和NF-κB信号通路的激活。结论Genkwanin通过抑制JAK / STAT和NF-κB信号通路的激活，对AIA大鼠具有抗类风湿关节炎的作用。在这项工作中获得的结果使我们建议，Genkwanin可能在先前证明的根氏黄酮类黄酮提取物（即FFD）的抗类风湿关节炎活性中起关键作用。
更新日期：2019-08-01
中文翻译：
Genkwanin通过抑制JAK / STAT和NF-κB信号通路来改善大鼠佐剂性关节炎。
背景技术Genkwanin是从传统中草药Daphne genkwa中分离出来的一种黄酮。我们以前的工作证明，从D. genkwa（FFD）中分离出的四种类黄酮（包括genkwanin）可以显着改善大鼠模型的关节炎症状。最近的研究表明，genkwanin表现出抗炎和免疫调节活性，这两者与类风湿关节炎（RA）的病理密切相关。因此，研究Genkwanin的抗RA作用及其机制可能使我们更深入地了解FFD对RA的治疗作用。目的本研究旨在研究Genkwanin对大鼠佐剂诱发的关节炎（AIA）模型的抗类风湿关节炎的活性，并探讨其潜在机制。方法在AIA大鼠模型上，通过测定爪肿胀程度和关节炎指数评分以及关节组织的组织病理学分析，评估Genkwanin的抗类风湿关节炎活性。用ELISA法测定血清细胞因子水平，用Griess法测定血清NO水平。通过蛋白质印迹分析和免疫组化分析确定JAK / STAT和NF-κB信号通路中蛋白质的表达和磷酸化水平。结果Genkwanin显着降低了AIA大鼠的爪肿胀和关节炎指数，还降低了关节组织的炎症和骨破坏。用Genkwanin处理后，血清TNF-α，IL-6和NO的浓度显着降低，而IL-10的浓度显着升高。Genkwanin抑制AIA大鼠滑膜组织中JAK / STAT和NF-κB信号通路的激活。结论Genkwanin通过抑制JAK / STAT和NF-κB信号通路的激活，对AIA大鼠具有抗类风湿关节炎的作用。在这项工作中获得的结果使我们建议，Genkwanin可能在先前证明的根氏黄酮类黄酮提取物（即FFD）的抗类风湿关节炎活性中起关键作用。
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