title: Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius.
abstract: The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED (50) = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED (50) = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO (3) + NO (2)) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H (+),K (+)-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC (50) = 212 microg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg ( p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.
authors.affiliation: Department of Pharmacology, Biological Sciences Sector, Universidade Federal of Paraná, Curitiba, Brazil.
authors.forename: Cristiane Hatsuko
authors.initials: CH
authors.lastname: Baggio
authors.forename: Glaucia
authors.initials: G
authors.lastname: De Martini Otofuji
authors.forename: Wesley Mauricio
authors.initials: WM
authors.lastname: de Souza
authors.forename: Cid Aimbiré
authors.initials: CA
authors.lastname: de Moraes Santos
authors.forename: Luce Maria Brandao
authors.initials: LM
authors.lastname: Torres
authors.forename: Lia
authors.initials: L
authors.lastname: Rieck
authors.forename: Maria Consuelo
authors.initials: MC
authors.lastname: de Andrade Marques
authors.forename: Sonia
authors.initials: S
authors.lastname: Mesia-Vela
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D029062:Apocynaceae; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005744:Gastric Acid / Q000378:metabolism; D005769:Gastrointestinal Motility; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008026:Ligation; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D026121:Indole Alkaloids; D010936:Plant Extracts; D000431:Ethanol