Efeito antinociceptivo do extrato de Cissus gongylodes (Baker) Planch., da substância isolada (ácido málico) e a participação do sistema canabinoide e da via NO/GMPc/KATP

Abstract

Cupá - Cissus gongylodes (Baker) Planch - is a cosmopolitan vine, found in Brazil in several states, including Minas Gerais. It is been said that cupá has pain-relieving properties, so this study aimed to demonstrate its analgesic potential, in order to validate traditional knowledge and elucidate the pharmacological pathway that participates in this event. Male Swiss mice (30g - 40g, n = 5) were used. The antinociceptive action of EE was assessed by the formalin test. The animals were submitted to oral pretreatment with diluted extract in concentrations 0, 10, 30, 100, 300 and 1000 mg / kg (extract / animal weight), one administration. 2% formalin - hyperalgesic agent - was administered at the paw and licking time was recorded through periods of nociceptive pain, 0-5 min after formalin, and inflammatory pain, 15-30 min. EE demonstrated a dose-dependent antinociceptive effect. Five fractions of this extract (F1, F2, F3, F4 and F5) were tested, using the paw withdrawal test submitted to compression on the analgesimeter, with the hyperalgesic prostaglandin E2 (PGE2), to assess the nociceptive threshold. F1 obtained more satisfactory results and, therefore, subjected to a chemical characterization identifying malic acid as the major compound of the fraction. Pure L-malic acid and DL-malic acid (racemic mixture) were also tested using the paw withdrawal method (50, 100 and 200 μg/paw). L-malic acid showed the best dose-dependent antinociceptive effect profile, with 100 μg sufficient for the maximum effect. We did not see the participation of the opioidergic system in antinociception by L-malic 100 μg. However, we verified the involvement of cannabinoidergic CB1 receptors and endocannabinoid anandamide (AEA). We also verified the participation of the NO/cGMP/KATP channels in the antinociceptive effect of L-malic, through the use of specific inhibitors and blockers. We suggest that L-malic acid could be a new indication for possible therapeutic use for the treatment of common pain.