title: Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice.
abstract: This study investigates the gastroprotective effects of hecogenin, a steroid saponin isolated from Agave sisalana, on experimental models of gastric ulcer. Male Swiss mice were used in the models of ethanol- and indometacin-induced gastric ulcer. To clarify the hecogenin mechanism of action, the roles of nitric oxide (NO), sulfhydryls (GSH), K⁺(ATP) channels and prostaglandins were also investigated, and measurements of lipid peroxidation (TBARS assay) and nitrite levels in the stomach of hecogenin-treated and untreated animals were performed. Furthermore, the effects of hecogenin on myeloperoxidase (MPO) release from human neutrophils were assessed in vitro. Our results showed that hecogenin (3.1, 7.5, 15, 30, 60 and 90 mg/kg, p.o.) acutely administered, before ethanol or indomethacin, exhibited a potent gastroprotective effect. Although the pretreatments with L-NAME, an iNOS inhibitor, and capsazepine, a TRPV1 receptor agonist, were not able to reverse the hecogenin effect, this was reversed by glibenclamide, a K⁺(ATP) blocker, and indomethacin in the model of ethanol-induced gastric lesions. The hecogenin pretreatment normalized GSH levels and significantly reduced lipid peroxidation and nitrite levels in the stomach, as evaluated by the ethanol-induced gastric lesion model. The drug alone increased COX-2 expression and this effect was further enhanced in the presence of ethanol. It also decreased MPO release and significantly protected the gastric mucosa. In conclusion, we showed that hecogenin presents a significant gastroprotective effect that seems to be mediated by K⁺(ATP) channels opening and the COX-2/PG pathway. In addition, its antioxidant and anti-inflammatory properties may play a role in the gastroprotective drug effect.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo, 1127, CEP 60.431-270, Fortaleza, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Santos Cerqueira
authors.forename: Gabriela
authors.initials: G
authors.lastname: dos Santos e Silva
authors.forename: Emiliano
authors.initials: E
authors.lastname: Rios Vasconcelos
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fragoso de Freitas
authors.forename: Brinell
authors.initials: B
authors.lastname: Arcanjo Moura
authors.forename: Danielle
authors.initials: D
authors.lastname: Silveira Macedo
authors.forename: Augusto
authors.initials: A
authors.lastname: Lopes Souto
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa Filho
authors.forename: Luzia Kalyne
authors.initials: LK
authors.lastname: de Almeida Leal
authors.forename: Gerly Anne
authors.initials: GA
authors.lastname: de Castro Brito
authors.forename: Caden
authors.initials: C
authors.lastname: Souccar
authors.forename: Glauce Socorro
authors.initials: GS
authors.lastname: de Barros Viana
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007213:Indomethacin; D054086:KATP Channels / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011897:Random Allocation; D012502:Sapogenins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects* / Q000276:immunology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D054086:KATP Channels; D011453:Prostaglandins; D012502:Sapogenins; D009569:Nitric Oxide; D000431:Ethanol; C007908:hecogenin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D005978:Glutathione; D007213:Indomethacin