Análise toxicológica, anti-inflamatória e anti-nociceptiva do extrato etanólico e frações obtidas das folhas de Piper glabratum Kunth

Abstract

Inflammation and pain are present in various diseases such as diabetes, cancer, rheumatoid arthritis and dyslipidemias. Medicinal plants are important for scientific research and development of new pharmacological therapies. Among them, Piper glabratum, for its popular use in the treatment of wounds and edemas, already possessing scientific evidences of anti inflammatory and analgesic effect. The objective of this study was to evaluate the toxicity, anti inflammatory and anti-nociceptive activity of the ethanolic extract of P. glabratum (EEPG) leaves and the hexanic (HXPG) and hydroalcoholic fractions (HAPG) obtained from the extract, in experimental models in animals. The toxicological evaluation was carried out from acute toxicity and genotoxicity tests, in addition to the evaluation of the chemopreventive potential of the ethanolic extract. The low toxicity of the extract was demonstrated, with the DL50 higher than 2000 mg/kg, and a possible chemopreventive effect of the extract against DNA damage inducing agents. The phytochemical analysis of HXPG, performed by silica column chromatography and preparative thin-layer chromatography, showed the presence and isolation of Fitol (17mg) and a mixture of stigmellastrol and β-sitosterol (14mg). HAPG on reverse phase chromatography (C18), demonstrated the presence of two compounds of the class of glycosylated flavonols. The biological potential was determined by the tests of pleurisy and paw edema induced by carrageenan, spontaneous pain induced by formalin and zymosan induced joint inflammation, being observed the spontaneous mechanical and thermal nociceptive response to cold, formation of edema, leukocyte migration and exudation protein. It can be observed that in the carrageenan-induced pleurisy model, all treatments, but not the 30 mg/kg dose of EEPG, reduced the leukocyte migration and only the 300 mg/kg dose of EEPG and HXPG (19.5 mg/kg ) reversed protein exudation. The EEPG (30, 100 and 300 mg/kg), HXPG and HAPG (83.37 mg/kg) decreased edema, mechanical and thermal hyperalgesia in the carrageenan-induced paw edema model, with emphasis on HXPG and dose of 300 mg/kg of EEPG. In the spontaneous pain model, EEPG (300 mg/kg), HXPG and HAPG, prevented cold edema and allodynia, but only HXPG reduced spontaneous pain. The 300 mg/kg treatments of EEPG and HXPG were tested against zymosan -induced joint inflammation, where both reduced the formation of edema, mechanical hyperalgesia and leukocyte migration in a very similar way. We conclude that the EEPG and fractions have anti-inflammatory and analgesic activity, and that this pharmacological action may be related to the up-regulation of NFκB, induced by the presence of phytol, stigmasterol and β-sitosterol found in the hexane fraction.