Department of Clinical Analysis, Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-970, Brazil.
Pharmacol Rep. 2013;65(5):1263-71. doi: 10.1016/s1734-1140(13)71484-1.
Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan.
DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction.
DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01).
DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.
二氢可待因醇（DHC）是从 Esenbeckia leiocarpa Engl. 中分离出来的一种生物碱化合物，在实验模型中表现出抗炎特性。本研究旨在探讨 DHC 的化学结构修饰是否会改变其在卡拉胶诱导的胸膜炎小鼠模型中的抗炎作用。
从 Esenbeckia leiocarpa Engl. 中分离出 DHC。采用毛细管电泳、物理特性、红外分析产生的光谱数据以及核磁共振((1)H 和 (13)C)和质谱分析鉴定并阐明 DHC 结构。DHC 化合物通过亲核取代反应进行化学结构修饰，得到五种类似物：乙酰基（1）、对甲基苯甲酰基（2）、苯甲酰基（3）、对甲氧基苯甲酰基（4）和对氯苯甲酰基（5）。整个实验过程中使用瑞士小鼠。在胸膜炎诱导后 4 小时，定量测定小鼠胸腔积液中的炎症参数白细胞迁移、渗出物浓度和髓过氧化物酶（MPO）活性。
DHC 及其类似物乙酰基、对甲基苯甲酰基、苯甲酰基、对甲氧基苯甲酰基和对氯苯甲酰基均抑制总白细胞和白细胞分类迁移以及 MPO 活性（p<0.05）。只有 DHC 显著降低渗出物浓度（p<0.01）。
DHC 作为一种抗炎剂在卡拉胶诱导的胸膜炎小鼠模型中比其类似物更有效。我们没有确定哪些物理化学修饰改变了 DHC 的抗炎作用，但这种作用可能是由于 DHC 碳 17 位上的羟基修饰所致。
