Avaliação da Atividade Antiulcerogênia do Extrato Etanólico Bruto e da Fase Hexânica de Hyptis suaveolens L Poi Maminaceae em Modelos Animais

Abstract

Aerial parts of Hyptis suaveolens (Lamiaceae), known as alfazema-brava , tapera-velha , erva-canudo , cheirosa and alfavacão , is used in traditional medicine to treat stomach ailments, inflammations and infections. The aim of this study was to evaluate the gastroprotection, wound healing and toxicity of Hyptis suaveolens, with a view to validate its efficacy, safety as well as to corroborate existing data. To this end, behavioral evaluation and acute toxicity study of the ethanol extract (EEtOH-Hs) and hexane fraction (FaHex-Hs) at a single dose of 2.000 mg/kg (p.o) was performed in mice. Pharmacological effects, in particular, the gastroprotective activities of EEtOH-Hs and FaHex-Hs were evaluated. Initial pharmacological screening was conducted with EEtOH-H, Hs-FaHex, dichloromethanic fraction (FaDCM-Hs) and ethyl acetate fraction (FaAE-Hs) against acidified ethanol-induced gastric ulcers. Acute gastric ulcers induced by ethanol, NSAIDs, immobilization and cold stress, at the were carried out at doses of 62.5, 125, 250 and 500 mg / kg (po), and at 250 mg/kg (id) in gastric juice containment by pylorus ligature and ischemia-reperfusion. To evaluate ulcer healing property of EEtOH-Hs and FaHex-Hs, acetic acid-induced ulcers experiment was realized. In addition the toxicity of EEtOH-Hs and FaHex-Hs by repeated dosing for 14 days was also assessed using acetic acid ulcer model. The antimicrobial effect against Helicobacter pylori bacterium was investigated by agar diffusion method. Gastric juice parameters were evaluated in the pylorus ligature assay. Next, was investigated participation of mucus, sulfhydryl groups and nitric oxide (NO) in the gastroprotection and determine endogenous antioxidants parameters through the levels of lipid peroxidation (LPO) and superoxide dismutase (SOD) activity in gastric mucosa following ulcers induction by ischemia-reperfusion. Oral administration of EEtOH-Hs caused hyperactivity in the animals. However, it caused no death to none of the animals. Thus it was not possible to determine LD 50. In this assay, no sign of toxicity was evidenced in animals treated with FaHex-Hs. In pharmacological screening, EEtOH-Hs, as well as all fractions studied (FaHex-Hs, FaDCM-Hs, FaAE-Hs) caused significant inhibitions of the ulcerative lesion index (ULI) in the acidified ethanol ulcer model, being that FaHex-Hs was the most effective. EEtOH-Hs and FaHex-Hs, significantly reduced ULI in all models tested. EEtOH-Hs and FaHex-Hs exhibited healing properties in the acetic acid model of ulcers. EEtOH-Hs and FaHex-Hs had no effect on the gastric juice parameters and left unaltered the levels of mucus of the gastric mucosa. However changes were observed in the ulcerative lesion area (U.L.A) with the use of sulfhydryl groups blocker, inhibition of lipid peroxidation and increased SOD activity in the gastric mucosa. Therefore, the antiulcerogenic effect of EEtOH-Hs and FaHex-Hs may involve antioxidant and cytoprotective mechanisms.