sapogenins and Stomach-Ulcer

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.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antioxidants; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Glutathione; Humans; Indomethacin; KATP Channels; Lipid Peroxidation; Male; Mice; Neutrophil Activation; Nitric Oxide; Prostaglandins; Random Allocation; Sapogenins; Stomach; Stomach Ulcer

Lyophilized aqueous extracts obtained from Agave americana L (Agavaceae) collected in the north of Sardinia were characterized with regard to their steroidal sapogenin content. Extracts of A. americana and genins isolated from them were evaluated for anti-inflammatory properties by testing their effects on carrageenin-induced edema. The effect of orally administered genins on gastric mucous membranes was also assessed. Lyophilized extracts administered by the intraperitoneal route at doses equivalent to 200 and 300 mg/kg of fresh plant starting material, showed good anti-inflammatory activity. Doses of genins (total steroidal sapogenins, hecogenin and tigogenin) equivalent to the amount in the lyophilized extracts produced an antiedentatous effect which was much stronger and more efficacious than that obtained with an i.p. administration of 5 mg/kg of indomethacin or dexamethasone 21-phosphate at a dose equivalent to the molar content of hecogenin administered. At the doses used to evaluate the anti-inflammatory activity, the genins did not have any harmful effect on the gastric mucous membranes. Lesions occurred when significantly higher doses of hecogenin were given, but gastric damage was still less than that caused by the drugs used for comparative purposes.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Gastric Mucosa; Inflammation; Italy; Male; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Sapogenins; Spirostans; Stomach Ulcer; Water

Hung, C.R., T.S. Wu and T.Y. Chang. The comparison between the effects of ethanol-extracted saikosaponin (SS) and 16, 16-dimethyl prostaglandin E2 (dmPGE2) on gastric acid back diffusion and mucosal damage induced by 100 mg/kg of acidified tannic acid (tannic acid dissolved in 100 mm HCl + 54 mM NaCl solution) was studied in the vagotomized rat. Crude saikosaponin (500 mg/kg) given by intragastric irrigation (I.G.) produced a significant inhibition (p < 0.05), while dmPGE2 (100 micrograms/kg) provoked a significant increase (p < 0.05) in acid back diffusion induced by acid solution. When graded doses of SS (100-1000 mg/kg) were added to acidified tannic acid solution and instilled to the stomach, a dose-dependent inhibition in acidified tannic acid-induced mucosal ulceration and acid back diffusion was achieved. The decrease in the H+ concentration and the increase in the Na+ concentration in the final samples induced by acidified tannic acid were also significantly (p < 0.05) inhibited by the same doses of SS. However, neither intraduodenal (I.D.) nor intravenous (i.v.) administration of SS was effective in inhibiting these ulcerogenic parameters. When dmPGE2 (3-100 micrograms/kg) was given concomitantly with acidified tannic acid solution, the acid back diffusion as well as mucosal ulceration provoked by acidified tannic acid were not significantly improved. The volume of luminal contents but not electrolyte concentrations in the final sample was considerably increased by adding dmPGE2 to the acidified tannic acid solution. The failure of I.D. or i.v. of dmPGE2 in inhibiting tannic acid-induced acid back diffusion and mucosal ulceration was also observed in other series of experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 16,16-Dimethylprostaglandin E2; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Diffusion; Electrolytes; Gastric Acid; Gastric Mucosa; Hydrolyzable Tannins; Male; Oleanolic Acid; Permeability; Rats; Rats, Sprague-Dawley; Sapogenins; Saponins; Stomach Ulcer; Vagotomy

The synthesis of hemisuccinates of some derivatives of oleanolic acid is reported, their inhibitory response to experimentally induced gastric ulcers in rats is examined. The hemisuccinates 13a (sodium salt of 13), 14 and 17 are more effective inhibitors than carbenoxolon-sodium.

Topics: Animals; Anti-Ulcer Agents; Male; Oleanolic Acid; Rats; Reserpine; Sapogenins; Stomach Ulcer; Structure-Activity Relationship