Evaluation of the antinociceptive properties of Hyptis crenata Pohl (Brazilian mint)

Abstract

This project aimed to investigate the main traditional use of the plant Hyptis crenata (HC) and evaluate its activity in a pre-clinical trial. A traditional use survey was carried out in two municipalities in Brazil, interviewing 20 people. The results showed that the main use of HC is for pain relief (19/20). The main method used for its preparation was decoction extract (11/20). The antinociceptive activity of HC decoction extract was evaluated showing that HC 15 mg/kg (p.o.) and HC 150 mg/kg (p.o.) increased delay in withdrawal response in the Hargreaves thermal withdrawal test by 29% and 28% respectively and decreased writhing occurrences induced by acetic acid by 70% and 71% (p<0.05), when compared to vehicle. These treatments were examined in the acetic acid writhing test for their effects on c-fos protein expression. The results showed that HC 150 mg/kg (p.o.) decreased c-fos expression in the hypothalamic paraventricular nucleus by 40% (p<0.05). This study also evaluated the HC doses 1 mg/kg (p.o.), 5 mg/kg (p.o.) and 45 mg/kg (p.o.) to assess the dose-response effect. HC dose- dependently induced antinociception in both animal models from 0 mg/kg (p.o.) to 15 mg/kg (p.o.), until a plateau response occurred between 15 mg/kg and 45 mg/kg (thermal withdrawal test p=0.0002 and writhing inhibition p=0.4725). Then, the decoction extract was fractionated and tested in an attempt to identify which HC compounds were active in inducing the antinociceptive effect. The hexane fraction had the highest activity (per dose) compared to the other fractions, indicating that it was enriched with the active compounds. Also, a preliminary COX inhibition assay was carried out; the results indicating possible COX-2 inhibition for HC treatments. Additionally, an investigation through behavioural analyses of whether HC and its fractions were affecting basal behaviour, such as muscle relaxation and sedation, showed no change of such behaviour. Overall, these data support the antinociceptive effect of Hyptis crenata and that there are specific compounds responsible for this effect.