Department of Integrated Chinese Traditional with Western Medicine, Peking University Health Science Center, Beijing 100191, PR China.
J Ethnopharmacol. 2011 Sep 1;137(1):774-82. doi: 10.1016/j.jep.2011.06.037. Epub 2011 Jul 2.
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.
To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol.
Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1β 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 (GRα) in synovium. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA).
Kirenol (1, 2, and 4 mg/kg) and prednisolone depressed paw swelling and reduced IL-1β of synovial fluid in the CIA rats (p<0.05 or p<0.01). Kirenol and prednisolone upregulated nuclear annexin-1 and inhibited NF-κB activity in synovium of CIA. The inhibitory effect of kirenol and prednisolone on NF-κB activity was enhanced by anti-annexin-1 Ab. Prednisolone, but not kirenol, downregulated plasma ACTH and GRα expression significantly (p<0.01).
Kirenol and prednisolone can upregulate nuclear annexin-1 which interacts with NF-κB to inhibit NF-κB 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.
京尼平是从中国夏枯草中分离得到的二萜类化合物。夏枯草数世纪以来一直被用于治疗关节炎，其安全性和疗效已通过长期的人类使用得到证实。
研究京尼平对胶原诱导性关节炎（CIA）的作用及其抗炎机制。
在 CIA 发病后，京尼平通过灌胃给予大鼠。通过爪肿胀和组织病理学评估病理变化。通过 ELISA 测定滑液中白细胞介素-1β（IL-1β）和血浆中促肾上腺皮质激素（ACTH）的浓度。通过 Western blot 检测滑膜中膜联蛋白-1（annexin-1）和糖皮质激素受体α（GRα）的表达。通过电泳迁移率变动分析（EMSA）评估 NF-κB DNA 结合活性。
京尼平（1、2 和 4mg/kg）和泼尼松龙可抑制 CIA 大鼠的爪肿胀并降低滑液中 IL-1β（p<0.05 或 p<0.01）。京尼平和泼尼松龙可上调 CIA 滑膜中的核 annexin-1 并抑制 NF-κB 活性。抗 annexin-1 Ab 增强了京尼平和泼尼松龙对 NF-κB 活性的抑制作用。泼尼松龙，但不是京尼平，可显著下调血浆 ACTH 和 GRα 的表达（p<0.01）。
京尼平和泼尼松龙可上调与 NF-κB 相互作用以抑制 NF-κB 活性的核 annexin-1，减少细胞因子的表达，从而减轻 CIA 关节的炎症。京尼平不会导致 ACTH 或 GR 下调，这与经典的糖皮质激素泼尼松龙不同。京尼平与 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。
