Avaliação farmacológica e toxicológica do extrato etanólico e de amidas das folhas de Piper amalago em modelos experimentais com roedores

Abstract

Piper amalago, also popularly known as "jaborandi" or "pariparoba", is used in folk medicine as analgesic, anti-inflammatory and for other pathophysiologies of the urinary tract. The objective of this study was to evaluate the antinociceptive, antihyperalgesia, antiarthritic, anti-inflammatory, antimycobactericidal activities of the amalago ethanolic extract (EEPA) and amides (N- [7- (3 ', 4' - metilenodioxifenil) -2 (Z), 4 (Z) -heptadienoyl] pirrolidina (1) e cloridrato de N- [7- (3 ', 4'-metilenodioxifenil) -2 (E), 4 (E) -heptadienoyl] pirrolidina (2) obtained from P. amalago in rodents and their possible mutagenic and genotoxic effects. The rats or mice were orally treated with EEPA (100 mg / kg) or amides 1 and 2 (1 or 3 mg/kg), and could be single or multiple doses for 20 days, depending on the pain induction model, which were performed Complete Freund's Adjuvant (CFA), sciatic nerve injury (SNI), carrageenan-induced hyperalgesia, or formalininduced nociception. A model of inflammation, spreading and production of nitric oxide (NO) in macrophages culture, BCG induced pleurisy, mutagenic and genotoxic tests such as comet, micronucleus, phagocytic activity and assay apoptosis. The results showed that EEPA inhibited mechanical hyperalgesia, knee edema and heat hyperalgesia, but not the depressive behavior induced by intraplantar CFA injection. EEPA inhibited mechanical and cold hyperalgesia in the SNI model, and amides 1 and 2 prevented mechanical hyperalgesia induced by carrageenan and antinociceptive effects in both phases of the formalininduced model. EEPA and 1 promoted a reduction in the spreading and in the production of NO stimulated in macrophages. They significantly reduced the total number of leukocytes induced by BCG, and EEPA did not present genotoxic or mutagenic effects. It is concluded that P. amalago was effective for the inhibition of pain, showing a natural anti-inflammatory agent, antimycobacterial and without genotoxic effects in comets and micronuclei. The amides obtained may be the active principle (s) present in the EEPA.