Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its β-Cyclodextrin (β-CD) Inclusion Complex in Animal Inflammation Models

• Main Authors: Andreza Guedes Barbosa Ramos, Irwin Rose Alencar de Menezes, Maria Sanádia Alexandre da Silva, Renata Torres Pessoa, Luiz Jardelino de Lacerda Neto, Fabíola Rocha Santos Passos, Henrique Douglas Melo Coutinho, Marcello Iriti, Lucindo José Quintans-Júnior
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Foods
• Subjects: terpenes; antiedematogenic effect; interleukin; tumor necrosis factor
• Online Access: https://www.mdpi.com/2304-8158/9/5/630

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.