Paulino Niraldo, Abreu Sheila Rago Lemos, Uto Yoshihiro, Koyama Daisuke, Nagasawa Hideko, Hori Hitoshi, Dirsch Verena M, Vollmar Angelika M, Scremin Amarilis, Bretz Walter A
Programa de Pós-graduação em Farmácia, Universidade Bandeirante de São Paulo, São Paulo, Brazil.
Eur J Pharmacol. 2008 Jun 10;587(1-3):296-301. doi: 10.1016/j.ejphar.2008.02.067. Epub 2008 Feb 29.
Artepillin C is the major compound in the Brazilian green propolis from Baccharis dracunculifolia. Our aim in this study was to investigate the anti-inflammatory effects, absorption, and bioavailability of Artepillin C in mice. The animals used were male Swiss mice subjected to: paw oedema by carrageenan (300 microg/paw), carrageenan-induced peritonitis, and prostaglandin E(2) determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-kappaB activity in HEK 293 cells. Finally, we measured the absorption and bioavailability of Artepillin C in plasma from mice by means of GC-MS after a single oral dose (10 mg/kg). In vivo, Artepillin C produced a maximal inhibition of 38% after 360 min on paw oedema. Artepillin C also decreased the number of neutrophils during peritonitis (IC(50): 0.9 (0.5-1.4) mg/kg). Treatment with Artepillin C decreased prostaglandin E(2) by 29+/-3% and 58+/-5% at 1 and 10 mg/kg, respectively, with a mean ID(50) of 8.5 (8.0-8.7) mg/kg). Similarly, in in vitro models, Artepillin C (3, 10, or 100 microM) decreased nitric oxide production by RAW 264.7 cells with a mean IC(50) of 8.5 (7.8-9.2) microM. In HEK 293 cells, Artepillin C reduced NF-kappaB activity with a mean IC(50) of 26 (22-30) mug/ml), suggesting anti-inflammatory activity, particularly during acute inflammation. Lastly, Artepillin C was absorbed after an oral dose (10 mg/kg) with maximal peaks found at 1 h (22 microg/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E(2) and nitric oxide inhibition through NF-kappaB modulation, and exhibited bioavailability by oral administration.
阿替匹林C是来自巴西龙蒿叶芽孢杆菌的绿色蜂胶中的主要化合物。本研究的目的是探讨阿替匹林C在小鼠体内的抗炎作用、吸收情况和生物利用度。所用动物为雄性瑞士小鼠，进行以下实验：角叉菜胶致爪肿胀（300微克/爪）、角叉菜胶诱导的腹膜炎以及前列腺素E2测定。我们还在体外测定了RAW 264.7细胞产生一氧化氮的情况以及HEK 293细胞中核因子κB的活性。最后，在单次口服剂量（10毫克/千克）后，通过气相色谱-质谱法测定了小鼠血浆中阿替匹林C的吸收情况和生物利用度。在体内，阿替匹林C在360分钟时对爪肿胀产生了最大38%的抑制作用。阿替匹林C还减少了腹膜炎期间中性粒细胞的数量（半数抑制浓度：0.9（0.5 - 1.4）毫克/千克）。阿替匹林C治疗在1毫克/千克和10毫克/千克时分别使前列腺素E2降低了29±3%和58±5%，平均半数抑制剂量为8.5（8.0 - 8.7）毫克/千克。同样，在体外模型中，阿替匹林C（3、10或100微摩尔）降低了RAW 264.7细胞产生一氧化氮的量，平均半数抑制浓度为8.5（7.8 - 9.2）微摩尔。在HEK 293细胞中，阿替匹林C降低了核因子κB的活性，平均半数抑制浓度为26（22 - 30）微克/毫升，表明具有抗炎活性，尤其是在急性炎症期间。最后，口服剂量（10毫克/千克）的阿替匹林C被吸收，在1小时时出现最大峰值（22微克/毫升）。总体而言，阿替匹林C显示出抗炎作用，至少部分是通过调节核因子κB抑制前列腺素E2和一氧化氮介导的，并且口服给药具有生物利用度。
