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.

Saponins of Agave: Chemistry and bioactivity

“…The effect of hecogenin (1) was attributed to opening of K þ ATP channels and prostaglandin synthesis. It also showed antiinflammatory activity by decreasing release of myeloperoxidase from human neutrophils in vitro (Cerqueira et al, 2012).…”

Anti-Inflammatory Potential of Hecogenin in Experimental Animals: Possible Involvement of Inflammatory Cytokines and Myeloperoxidase

“…Their protective effects are not due to the inhibition of gastric acid secretion, but possibly to the activation of protective factors present in the mucous membrane [15]. The documented reports of shown the effect of HG on oxidative stress, lipid peroxidation and myeloperoxidase, a biomarker of inflammation, as well as its gastric ulcer protective effect was confirmed with histological and COX-2 immunohistochemistry studies [20]. Fluticasone propionate (androstane nucleus) is a topically active corticosteroid molecule [21].…”

“…Hecogenin (Steroidal sapogenin) is the most ubiquitous glycoside isolated from leaves of various Agave genus species, has anti-inflammatory effects. It is traditionally used for immunomodulatory [45], anthelmintics [46], analgesic, anti-inflammatory activity [47], hepatoprotective, antiulcer activity [21] and antimicrobial activity [48]. There are very few studies showing the anti-inflammatory activity of hecogenin [47,49].…”

Saponins and Sapogenins of Agave With Respect to Diverse Pharmacological Role of Hecogenin

“…In addition to this, hecogenin exhibits variety of important biological activities in the pharmaceutical industry [12,13]. The steroidal sapogenins (hecogenin) from Agave genus were reported to have a number of pharmacological activities such as anti-inflammatory, analgesic, antiarthritis, gastroprotective, anticancer and larvicidal activity [14][15][16][17][18]. Overall, the results of numerous pharmacological studies have been linking the possible use of hecogenin as a novel multi-target based therapeutic agent against abundant long-lasting disease conditions.…”

“…These gastroprotective effects were confirmed by histological data of hecogenin in ethanol induced gastric ulcer in rats. The probable mechanism behind the gastroprotective activity would be antioxidant properties, generation of free radicals by increasing the glutathione level and the blockade of lipoperoxidation [14] ( fig. 6).…”