Original Paper Pharmacology	Planta Med 2005; 71: 733-738 DOI: 10.1055/s-2005-871286
© Georg Thieme Verlag KG Stuttgart · New York
Gastroprotective Mechanisms of Indole Alkaloids from Himatanthus lancifolius
Cristiane Hatsuko Baggio1, Glaucia De Martini Otofuji1, Wesley Mauricio de Souza2, Cid Aimbiré de Moraes Santos2, Luce Maria Brandao Torres3, Lia Rieck1, Maria Consuelo de Andrade Marques1, Sonia Mesia-Vela1
1 Department of Pharmacology, Biological Sciences Sector, Universidade Federal of Paraná, Curitiba, Brazil 2 Department of Pharmacognosy, Health Sciences Sector, Universidade Federal of Paraná, Curitiba, Brazil 3 Department of Physiology, Institute of Botany, Sao Paulo, SP, Brazil

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 (ED₅₀ = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED₅₀ = 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 (NO₃ + NO₂) 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 (EC₅₀ = 212 µg/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.

Key words

Alkaloids - uleine - demethoxyaspidormine - antiulcer - medicinal plant - Himatanthus