In-silico and in-vivo evaluation of the cardiovascular effects of five Leonotis leonurus diterpenes

Abstract

Leonotis leonurus extracts and compounds have been extensively studied for pharmacological effects. However, most of the diterpenes isolated from the plant have not been evaluated as possible contributors to the cardiovascular effects of the plant extracts. In this study, computational modelling was used to predict the drug-likeness and cardiovascular effects of five diterpenoids of L. Leonurus. The predicted results were then subsequently compared with results obtained from anaesthetized normotensive Wistar rats to determine the most likely lead compounds for drug development. Molecular operating environment (MOE) software was used to assess the drug-likeness and molecular docking interactions between the diterpenoids and the angiotensin-converting enzyme (ACE) (PDB; 2 × 8Z), the angiotensin receptor (AT1) (PDB; 3R8A) and the β1 receptor (PDB; 2Y04). The predicted cardiovascular effects were assessed in the anaesthetized normotensive Wistar rat model.