title: Gastroprotective effect of aparisthman, a diterpene isolated from Aparisthmium cordatum, on experimental gastric ulcer models in rats and mice.
abstract: Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae), known in the State of Pará, Brazil as "ariquena queimosa", is a medium-sized tree which is native to the North Brazilian coastal region. Previous phytochemical studies of the bark of A. cordatum yielded a furan diterpenoid with a clerodane skeleton, called aparisthman. Recently, we reported the antiulcerogenic activity of trans-dehydrocrotonin (DHC), a furan diterpene isolated from Croton cajucara bark, in different ulcerogenic models in mice and rats. The aim of the present study was to assess the possible antiulcerogenic activity of aparisthman. When previously administered (p.o.) at the dose of 100 mg/kg(-1), aparisthman reduced significantly (p < 0.01) gastric injury induced by the indomethacin/bethanechol (71%), ethanol (71%), pylorus ligature, (59%) and hypothermic restraint-stress models (50%), in mice and rats. In the HCl/ethanol-induced gastric ulcer model in mice, at oral doses of 100 and 250 mg/kg(-1), aparisthman from A. cordatum reduced significantly (p < 0.001) the formation of gastric lesions by 59% and 66%, respectively, as compared with control. In the pylorus-ligature model, aparisthman (p.o.) decreased the volume of gastric juice as compared with control (p < 0.001). When aparisthman (100 mg/kg(-1)) was administered intraduodenally to mice, significant modifications were found, such as a decrease in gastric acidity as compared with control. In the animals pre-treated with aparisthman, free mucus production increased by 19% in the gastric mucosa (p < 0.05). The results suggest that aparisthman from A. cordatum presents a significant anti-ulcer effect when assessed in these induced ulcer models. Although the mechanism underlying this antiulcerogenic effect remains unknown, it seems to be related to an increase of the defensive mechanisms of the stomach such as prostaglandin synthesis and mucus production. The good yield of aparisthman obtained from A. cordatum, as well as its antiulcerogenic activity, suggest that this compound should be submitted to pharmacological research as a potential new antiulcerogenic drug.
authors.affiliation: Inst. de Biologia e Saúde Pública, Fund. Universidade do Tocantins, Porto Nacional, Tocantins, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Hiruma-Lima
authors.forename: J S
authors.initials: JS
authors.lastname: Gracioso
authors.forename: W
authors.initials: W
authors.lastname: Toma
authors.forename: A B
authors.initials: AB
authors.lastname: Almeida
authors.forename: A C
authors.initials: AC
authors.lastname: Paula
authors.forename: D S
authors.initials: DS
authors.lastname: Brasil
authors.forename: A H
authors.initials: AH
authors.lastname: Muller
authors.forename: A R
authors.initials: AR
authors.lastname: Souza Brito
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001938:Brazil; D002927:Cimetidine / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D019665:Euphorbiaceae / Q000737:chemistry*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D064747:Lansoprazole; D008297:Male; D051379:Mice; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014197:Trees / Q000737:chemistry*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D010936:Plant Extracts; C434109:aparisthman; D064747:Lansoprazole; D002927:Cimetidine; D009853:Omeprazole; D007213:Indomethacin