title: Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.
abstract: BACKGROUND
  The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms.
  
  
  METHODS
  Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed.
  
  
  RESULTS
  The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H(+)], pH) did not show any alteration.
  
  
  CONCLUSIONS
  Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.
authors: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors: F F B P
authors: FF
authors: Freitas
authors: H B
authors: HB
authors: Fernandes
authors: C A
authors: CA
authors: Piauilino
authors: S S
authors: SS
authors: Pereira
authors: K I M
authors: KI
authors: Carvalho
authors: M H
authors: MH
authors: Chaves
authors: P M G
authors: PM
authors: Soares
authors: L M C V
authors: LM
authors: Miura
authors: J R S A
authors: JR
authors: Leite
authors: R C M
authors: RC
authors: Oliveira
authors: F A
authors: FA
authors: Oliveira
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D009093:Mucus / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013312:Stress, Physiological; D032106:Zanthoxylum / Q000737:chemistry
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054086:KATP Channels; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D009569:Nitric Oxide; D000431:Ethanol; D002374:Catalase; D019001:Nitric Oxide Synthase; D006851:Hydrochloric Acid; D007213:Indomethacin