MODULATION BY GLYCYRRHETINIC ACID-DERIVATIVES OF TPA-INDUCED MOUSE EAR EDEMA
MODULATION BY GLYCYRRHETINIC ACID-DERIVATIVES OF TPA-INDUCED MOUSE EAR EDEMA
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DOI：
10.1111/j.1476-5381.1989.tb11801.x
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发表时间：
1989-01-01
影响因子：
7.3
通讯作者：
KOSHIHARA, Y
中科院分区：
文献类型：
--
作者：
INOUE, H;MORI, T;KOSHIHARA, Y
研究了甘草次酸及其衍生物对TPA（12-O-十四烷酰佛波醇-13-乙酸酯）引起的小鼠耳水肿的抗炎作用。首先针对化学介质研究了 TPA 引起的耳水肿的机制。应用TPA（每耳2μg）后5小时，耳水肿的形成达到最大，并且小鼠耳的前列腺素E2（PGE2）的产生随着水肿的形成而增加。 TPA 治疗后 60 分钟内使用放线菌素 D 和放线菌酮（每耳分别 0.1 mg）可预防 TPA 引起的耳部水肿。在所检查的甘草次酸衍生物中，二半邻苯二甲酸酯衍生物（IIe、IIe''、IIIa、III''a、IVa、IVa''）对局部（ID50，IIe 每耳 1.6 mg，IIIa 每耳 2.0 mg，IVa 每耳 1.6 mg）和口服（ID50，88 mg kg-1）抑制耳水肿效果最强。 对于IIe”，对于IIIa”为130 mg kg-1，对于IVa”为92 mg kg-1)施用。在 TPA 治疗前 30 分钟施用甘草次酸 (Ia) 及其衍生物比在 TPA 治疗后 30 分钟施用更有效地抑制水肿。即使在 TPA 治疗前 3 小时使用，三萜化合物 IVa 的二半邻苯二甲酸酯也能完全抑制水肿。母体化合物甘草次酸 (Ia) 和脱氧甘草次醇 (IIa) 在口服剂量低于 200 mg kg-1 时几乎没有产生抑制作用。这些结果表明，通过化学修饰衍生自甘草次酸的三萜二半邻苯二甲酸酯衍生物可用于通过局部和口服应用治疗皮肤炎症。
The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. The formation of ear oedema reached a maximum 5 h after TPA application (2 .mu.g per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe'', IIIa, III''a, IVa, IVa'') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe'', 130 mg kg-1 for IIIa'' and 92 mg kg-1 for IVa'') administration. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application.