Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls

Abstract

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.

Gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean Lamiaceae <I>Sphacele chamaedryoides</I> (Balbis) Briq.

“…The spectroscopic data of diterpenes 1-7 and 10 are in agreement with those previously reported in the literature. (13,14,23,(30)(31)(32)(33)(34) The NMR data of the compounds 11-13 are in concordance with those reported by Ulubelen et al [35] and Agrawal. [36] Compound 13 The effect of the isolated compounds was assessed by oral administration using the HCl/EtOH-induced gastric lesion model in mice.…”

“…[7,8] The gastroprotective effect and cytotoxicity of abietane diterpenes has been shown in studies carried out with natural products as well as semisynthetic derivatives. The work performed so far includes the classical investigations leading to ecabet sodium, [9][10][11] structureactivity trends in dehydroabietic acid derivatives, [12] ferruginol [13][14][15] and its semisynthetic products, [16] cytotoxic effect of Salvia diterpenes [17] and a dehydroabietylamine derivative. [18] The genus Sphacele is commonly found in central Chile and it constitutes are a good source of diterpenes.…”

Qualea parviflora Mart.: An integrative study to validate the gastroprotective, antidiarrheal, antihemorragic and mutagenic action

“…The same results did not occur under treatments with vehicle and NSAID, since NSAID administration significantly diminished the PGE 2 levels in these groups to half those of the sham group (4.91 ± 1.11 pg/g protein). Diterpenes with gastroprotective effect that reduce gastric acid output and improve the antioxidant capacity of the gastric mucosa by maintaining the GSH levels and stimulating gastric PGE 2 synthesis were also detected by Areche et al (2008). Beyond the antiulcer effects of QP expressed by amplifying sulfhydryl compounds and GSH levels and elevating gastric mucosa PGE 2 levels, we also observed that the anti-Helicobacter pylori action exerted by QP was accomplished through an antidiarrheal effect.…”

Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

“…Both ethanol-induced decrease of nitric oxide (NO) production and release, and a decrease of calcitonin gene-related peptide (CGRP) secretion from afferent nerves in the gastric mucosa lead to disturbances in MBF (Sibilia et al 2007;Brzozowski et al 2003Brzozowski et al , 2008Szolcsányi and Barthó 2001). Ethanol-induced increased oxidative stress and decreased levels of PGs (COX-2 derived) delay mucosal cell proliferation (Hernández-Muñoz et al 2000;Areche et al 2008).…”