Efeito antinociceptivo e marcadores de estresse oxidativo do extrato enriquecido com alcaloides indólicos ativos das folhas de Tabernaemontana catharinensis

Abstract

Ethnopharmacology has been important for the identification of active compounds of natural products, mainly in plants. The pain can have diverse etiologies, with complex mechanisms, being correlated with more diverse pathologies. Pharmacological activities of Tabernaemontana catharinensis (Apocynaceae) have been evidenced as: antiofidic, antimicrobial, antioxidant, antitumor, bioinseticide, anti-inflammatory and antinociceptive. The objective of this work was to evaluate the antinociceptive potential and the modulation of the oxidative stress of the enriched extract of the indole alkaloids from leaves of Tabernaemonta catharinensis (AITc) in experimental models of nociception, oxidative stress and toxicology. The AITc extract was obtained by ultrasonic extraction followed by a liquid-liquid extraction from leaves of T. catharinensis. The chemical composition of the extract was determined by high resolution mass spectrometry. For the in vivo tests, male mice (Mus musculus) Swiss were used, the extract being administered in doses of 1,0, 5,0 and 10,0 mg / kg, in the following tests: acetic acid, formalin, tail-immersion, hot plate and open field, in which saline, morphine or diazepam groups were used depending on the test to be performed. The histopathological evaluation and oxidative stress markers were performed through the collection and evaluation of organs (spleen, kidneys, liver, brain, stomach). The results of this work evidenced in the chemical characterization the presence of 10 ibolan class Ibolan alkaloids (Ibogamine, Coronaridina and Voacristina); while another three (Affinisine, Voachalotine and 12-methoxy-Nb-methylvoachalotine), alkaloids belonging to the class of Corinanians.The extract in doses ranging from 5,0 to 10,0 mg / kg, showed antinociceptive effect in the acetic acid test, inhibiting in 47.7% and 61.6% respectively. In the formalin test, a reduction in the lymph time of the legs of 47.1% (1st stage) and 43.6% (2nd stage) was observed for a dose of 5,0 mg / kg. However, the tail-immersion and hot plate tests did not express changes in the latency period, whereas in the open field test, there were no changes in locomotor activity. The oxidative damage to the lipids was higher in the stomach, and a reduction of this parameter was found in the brain. No differences in nitric oxide levels and total antioxidant status were observed in any of the tissues studied. The toxicological, biochemical and hematological tests, as well as the histopathological tests, showed no adverse effects at the administered doses. In this way, the alkaloidal extract of T. catharinensis justifies the use of this plant in the popular medicine as analgesic, probably result of a mechanism of peripheral action however more experiments will be carried out in order to elucidate the exact mechanism. This study demonstrates that the AITc extract had no toxicity, guaranteeing safe use by the population.