Ramos Andreza Guedes Barbosa, de Menezes Irwin Rose Alencar, da Silva Maria Sanádia Alexandre, Torres Pessoa Renata, de Lacerda Neto Luiz Jardelino, Rocha Santos Passos Fabíola, Melo Coutinho Henrique Douglas, Iriti Marcello, Quintans-Júnior Lucindo José
Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil.
Department of Physiology, Federal University of Sergipe, São Cristóvão, Aracaju - SE 49100-000, Brazil.
Foods. 2020 May 14;9(5):630. doi: 10.3390/foods9050630.
Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a β-cyclodextrin-isopulegol inclusion complex (ISO/β-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/β-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/β-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1β and TNF-α. ISO and ISO/β-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in β-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.
异蒲勒醇（ISO）是一种醇类单萜，广泛存在于不同植物物种中，如香蜂草，并且已有报道称其具有多种药理特性。与其他萜类一样，ISO是一种高度挥发性化合物，微溶于水，因此将其包合到环糊精（CDs）中是提高其溶解度和生物利用度的一种有趣方法。因此，我们的目的是评估异蒲勒醇和β-环糊精-异蒲勒醇包合物（ISO/β-CD）在啮齿动物模型中的抗水肿和抗炎活性。对于抗炎活性评估，使用了抗水肿体积描记法以及急性（腹膜炎和胸膜炎）和慢性（棉球诱导肉芽肿）抗炎模型。对接程序用于评估、分析和预测它们与H1和Cox-2受体的相互作用结合模式。将动物（n = 6）分为几组：ISO组、ISO/β-CD组、阴性对照组（生理盐水）和阳性对照组（吲哚美辛和异丙嗪）。ISO和ISO/β-CD能够通过减少白蛋白外渗、白细胞迁移和MPO浓度以及降低IL-1β和TNF-α的渗出水平来降低急性炎症活性。ISO和ISO/β-CD在角叉菜胶和右旋糖酐诱导的爪水肿中显著抑制致水肿活性。此外，在异物性肉芽肿炎症模型中，鉴于肉芽肿的重量和蛋白质浓度较低，二者均显著减轻了慢性炎症过程。结果表明，将ISO包合到β-环糊精中可改善其药理特性，组胺和前列腺素途径可能是其抑制机制，并且还增强了这种萜类的抗炎特性。
