Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis
Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis
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DOI：
10.1016/j.ejphar.2008.02.067
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发表时间：
2008-06-10
影响因子：
5
通讯作者：
Bretz, Walter A.
中科院分区：
文献类型：
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作者：
Paulino, Niraldo;Abreu, Sheila Rago Lemos;Bretz, Walter A.
Artepillin C 是来自 Baccharis dracunculifolia 的巴西绿蜂胶中的主要化合物。我们本研究的目的是研究 Artepillin C 在小鼠体内的抗炎作用、吸收和生物利用度。使用的动物是雄性瑞士小鼠，进行：角叉菜胶引起的爪水肿(300μg/爪)、角叉菜胶诱导的腹膜炎和前列腺素E(2)测定。我们还测量了 RAW 264.7 细胞的体外一氧化氮产量和 HEK 293 细胞中的 NF-κ B 活性。最后，我们通过 GC-MS 测量了单次口服剂量（10 mg/kg）后 Artepillin C 在小鼠血浆中的吸收和生物利用度。在体内，Artepillin C 在 360 分钟后对爪子水肿产生最大抑制 38%。 Artepillin C 还可以减少腹膜炎期间中性粒细胞的数量 (IC(50)：0.9 (0.5-1.4) mg/kg）。 Artepillin C 治疗使前列腺素 E(2) 在 1 和 10 mg/kg 时分别降低 29 +/- 3% 和 58 +/- 5%，平均 ID(50) 为 8.5 (8.0-8.7)mg/kg)。同样，在体外模型中，Artepillin C（3、10 或 100 μM）可降低 RAW 264.7 细胞的一氧化氮生成，平均 IC(50) 为 8.5 (7.8-9.2) μM。在 HEK 293 细胞中，Artepillin C 降低 NF-κ B 活性，平均 IC(50) 为 26 (22-30) μg/ml），表明抗炎活性，特别是在急性炎症期间。最后，Artepillin C 在口服剂量 (10 mg/kg) 后被吸收，并在 1 小时内达到最大峰值 (22 μg/ml)。总的来说，Artepillin C 表现出至少部分由前列腺素 E(2) 介导的抗炎作用和通过 NF-κ B 调节抑制一氧化氮的作用，并通过口服给药表现出生物利用度。 (C) 2008 Elsevier B.V. 保留所有权利。
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 mu g/paw), carrageenan-induced peritonitis, and prostaglandin E(2) determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-kappa B 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 mu M) decreased nitric oxide production by RAW 264.7 cells with a mean IC(50) of 8.5 (7.8-9.2) mu M. In HEK 293 cells, Artepillin C reduced NF-kappa B activity with a mean IC(50) of 26 (22-30) mu g/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 mu g/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E(2) and nitric oxide inhibition through NF-kappa B modulation, and exhibited bioavailability by oral administration. (C) 2008 Elsevier B.V. All rights reserved.