Preparation, physicochemical characterization, docking and antiarrhythmic effect of D-limonene and D-limonene hydroxypropyl-β-cyclodextrin complex

D-limonene (D-LIM) is a monoterpene found mainly in the essential oil of citrus fruits. Cardiovascular effects of DLIM alone have been extensively demonstrated. Despite possessing important pharmacological effects, its chemical properties prevent its clinical application. This study aimed to produce and characterize hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complex with D-LIM, and to assess its cardiovascular effects in animal model of arrhythmia. The inclusion complex was prepared by the slurry complexation, and characterized using HPLC, PXRD, DSC, and H-1 NMR. Molecular docking was performed to analyze the interactions between the complex. The antiarrhythmic effect was assessed in an animal model of arrhythmia induced by Bay K 8644. The physicochemical characterization showed that the D-LIM + HP-beta-CD complex formation had a complexation efficiency of 79.96 +/- 0.24%, which was corroborated with all analysis performed. Docking showed that D-LIM interacts with HP-beta-CD through hydrophobic and van der Waals bonds, with binding affinity of -4.2 kcal/mol. D-LIM + HP-beta-CD complex (10 mg/kg, i.v.) significantly reduced arrhythmias, reducing arrhythmia score (p < 0.01), duration of arrhythmias (p < 0.05) and prevented tachycardia (p < 0.05). Our results showed an efficient method of complexation of D-LIM + HP-beta-CD and improved its cardiovascular effects compared to D-LIM.

Automated summary

This study prepared and characterized an inclusion complex of D-LIM and HP-beta-CD and evaluated its cardiovascular effects in an animal model of arrhythmia. The results demonstrated that the D-LIM + HP-beta-CD complex significantly reduced arrhythmias, decreased the duration of arrhythmias, and prevented tachycardia.