Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice

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. (C) 2012 Elsevier B. V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Ceara, Dept Physiol & Pharmacol, BR-60431270 Fortaleza, Ceara, BrazilUniv Fed Ceara, Dept Pharm, BR-60431270 Fortaleza, Ceara, BrazilUniv Fed Paraiba, Dept Pharmaceut Sci, BR-58100000 Joao Pessoa, Paraiba, BrazilUniv Fed Ceara, Dept Morphol, BR-60431270 Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04044020 São Paulo, BrazilWeb of Scienc

AlteraÃÃes comportamentais, neuroquÃmicas e glicolipÃdicas em ratos tratados com Hoodia gordonii, um supressor natural do apetite

Hoodia gordonii à uma planta da famÃlia das apocinÃceas. OriginÃria do sudeste da Ãfrica, onde tem sido historicamente usada para suprimir o apetite durante longas jornadas de caÃa, sendo utilizada em diversos paÃses com o objetivo de emagrecer. No Brasil foi retirada do mercado devido à falta de estudos que comprovem sua eficÃcia e seguranÃa para o uso. O objetivo deste trabalho foi avaliar as alteraÃÃes comportamentais, neuroquÃmicas e glicolipÃdicas em ratos tratados com Hoodia gordonii. Para a realizaÃÃo deste estudo H. gordonii foi administrada por via oral nas doses de 25 e 50 mg/Kg durante oito dias consecutivos em ratos Wistar machos (160-200g), D-anfetamina 2 mg/Kg foi administrada intraperitonealmente de forma aguda e usada como padrÃo positivo. Os testes aconteceram 60 minutos apÃs o ultimo dia de tratamento com a Hoodia e 30 minutos apÃs o tratamento com D-anfetamina. Foram avaliados a variaÃÃo de peso dos animais durante o tratamento, bem como o consumo de Ãgua e comida. Para os testes comportamentais foram feitos os testes de labirinto em cruz elevado, campo aberto e placa perfurada. Para os estudos neuroquÃmicos foi feito HPLC com detecÃÃo eletroquÃmica. Para os testes glicolipÃdicos foi feita dosagem de Glicose, HDL, LDL, TG, colesterol total, ALT e AST. Os resultados mostraram que H. gordonii à capaz de reduzir o ganho de massa corpÃrea, bem como reduzir o consumo de comida e Ãgua. Os resultados dos testes comportamentais mostraram que ela à capaz de reduzir os parÃmetros observados no teste do labirinto em cruz e placa perfurada sem mostrar alteraÃÃo significante no campo aberto. Os resultados dos experimentos neuroquÃmicos evidenciaram um aumento do conteÃdo de noradrenalina e dopamina em corpo estriado de ratos, detectados eletroquimicamente pelo HPLC. Nos testes bioquÃmicos foi visto que ela tem a capacidade de reduzir os nÃveis de glicose, bem como a concentraÃÃo de triglicerÃdeos e colesterol total em soro de ratos, sem mostrar alteraÃÃo significante da ALT e AST. Foi possÃvel concluir que H. gordonii à capaz de reduzir a ingestÃo de alimentos e que este efeito pode estar de alguma forma ligado à neurotransmissÃo noradrenÃrgica e dopaminÃrgica, possuindo tambÃm atividade ansiogÃnica evidenciada pelos estudos comportamentais.Hoodia gordonii is a plant of the family apocinaceae. Originally from southeastern Africa, where it has historically been used to suppress appetite during long hunting trips, being used in several countries in order to lose weight. In Brazil was withdrawn from the market due to lack of studies proving its efficacy and safety for use. The aim of this study was to evaluate the behavioral changes and neurochemical glicolipÃdicas in rats treated with Hoodia gordonii. For this study H. gordonii was administered orally at doses of 25 and 50 mg/kg for eight consecutive days in male Wistar rats (160-200g), D-amphetamine 2 mg/kg was intraperitoneally administered acutely and used as a positive standard. The tests took place 60 minutes after the last day of treatment with the Hoodia and 30 minutes after treatment with D-amphetamine. We evaluated the weight change of the animals during treatment, as well as the consumption of water and food. For behavioral tests were performed tests elevated plus-maze, open field and hole board. For neurochemical studies was done HPLC with electrochemical detection. For testing was done glycolipid glucose, HDL, LDL and TG, total cholesterol, ALT and AST. The results showed that H. gordonii is capable of reducing body mass gain and reduce the consumption of food and water. The results of behavioral tests showed that it is able to reduce the parameters observed in the plus-maze test and hole board showing no significant change in the open field. The results of experiments showed an increase in the neurochemical content of noradrenaline and dopamine in the striatum of rats electrochemically detected by HPLC. In biochemical tests it was seen that it has the ability to lower blood glucose levels as well as the concentration of triglycerides and total cholesterol in serum from mice, showing no significant change in ALT and AST. It was concluded that H. gordonii is able to reduce food intake, and this effect may be somehow linked to the dopaminergic and noradrenergic neurotransmission, having also anxiogenic activity evidenced by behavioral studies