Kirenol upregulates nuclear Annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats
Kirenol upregulates nuclear Annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats
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DOI：
10.1016/j.jep.2011.06.037
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发表时间：
2011-09-01
影响因子：
5.4
通讯作者：
Qian, Rui-Qin
中科院分区：
文献类型：
--
作者：
Wang, Zhe-Ming;Zhu, Shi-Gong;Qian, Rui-Qin
民族药理意义：麒麟醇是从中国五味子属植物中提纯的一种二萜化合物。百合花被用于治疗关节炎已有数百年的历史，其安全性和有效性在人类漫长的使用历史中得到了证明。目的：探讨香草素对胶原诱导性关节炎(CIA)的影响及其抗炎机制。材料与方法：大鼠CIA发病后，灌胃给予香草素。通过足爪肿胀和组织病理学评价大鼠的病理变化。采用双抗体夹心法测定滑液中IL-1β浓度和血浆中促肾上腺皮质激素(ACTH)浓度。Western印迹法检测Annexin-1和糖皮质激素受体α(GRα)在滑膜中的表达。结果：Kirenol(1，2，4 mg/kg)和强的松龙可抑制CIA大鼠足爪肿胀，降低滑液中IL-1β的含量(p<；0.05或p<；0.01)。Kirenol和强的松龙上调CIA滑膜核膜联蛋白-1(Annexin-1)并抑制其核转录因子-kappaB的活性。抗Annexin-1抗体可增强Kirenol和强的松龙对NF-kappaB活性的抑制作用。强的松龙可显著下调血浆ACTH和GRα的表达(p<；0.01)。结论：强的松龙和强的松龙可上调核膜联蛋白-1的表达，从而抑制核因子-kappaB的活性，减少细胞因子的表达，从而减轻CIA关节的炎症。与经典的糖皮质激素强的松龙不同，Kirenol不会导致ACTH或GR下调。Kirenol与GCs具有相似的抗炎机制，但绕过了GCs治疗的相当大的局限性。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use. Aim of the study: To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of Kirenol.Materials and methods: Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1 beta in synovial fluid and adrenal corticotropin (ACTH) in plasma were determined by Elisa. Western blot was performed to detect the expression of Annexin-1 and glucocorticoid receptor alpha (GR alpha) in synovium. NF-kappa B DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA).Results: Kirenol (1, 2, and 4 mg/kg) and Prednisolone depressed paw swelling and reduced IL-1 beta of synovial fluid in the CIA rats (p < 0.05 or p < 0.01). Kirenol and Prednisolone upregulated nuclear Annexin-1 and inhibited NF-kappa B activity in synovium of CIA. The inhibitory effect of Kirenol and Prednisolone on NF-kappa B activity was enhanced by anti-Annexin-1 Ab. Prednisolone, but not Kirenol, downregulated plasma ACTH and GR alpha expression significantly (p < 0.01).Conclusion: Kirenol and Prednisolone can upregulate nuclear Annexin-1 which interacts with NF-kappa B to inhibit NF-kappa B activity, reduce cytokines expression and thereby attenuate inflammation of CIA joints. Kirenol does not lead to ACTH or GR downregulation, which is in contrast to classic glucocorticoid Prednisolone. Kirenol shares with GCs similar anti-inflammatory mechanism but bypass the considerable limitation of GCs treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved.