capsazepine and Stomach-Ulcer

This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α

Topics: Animals; Antioxidants; Capsaicin; Chromatography, High Pressure Liquid; Chronic Disease; Disease Models, Animal; Ericales; Ethanol; Female; Flavonoids; Gastrointestinal Motility; Glyburide; Histamine; Indomethacin; Male; Mice; Mucus; Naloxone; NG-Nitroarginine Methyl Ester; Phenols; Phytotherapy; Plant Extracts; Plant Leaves; Protective Agents; Stomach Ulcer; Water; Yohimbine

The antioxidizing properties of curcumin, a highly pleiotropic substance used for centuries in traditional medicine has been confirmed by numerous experimental and clinical studies. Curcumin exhibits anti-inflammatory, antiproliferative and anti-angiogenic actions inhibiting the development and progression of tumors but the efficacy of this compound to influence gastric acid secretion n in the stomach and to affect the gastric mucosal damage induced by non-topical ulcerogenes such as stress has been little studied. We determined the effect of curcumin on basal and pentagastrin- or histamine-stimulated gastric secretion, in rats with surgically implemented gastric fistulas and we assessed the contribution of gastric secretion, endogenous prostaglandin (PG), endogenous nitric oxide (NO), as well as sensory afferent nerves in the mechanisms underlying the potential gastroprotective effects of curcumin against stress-induced gastric mucosal lesions. Rats exposed to water immersion and restraint stress (WRS) for 3.5 h were pretreated either with: 1) vehicle (saline); 2) curcumin (2.5 - 100 mg/kg i.g.) or 3) curcumin (50 mg/kg i.g.) combined with or without indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.) or rofecoxib (10 mg/kg i.g.); 4) curcumin (50 mg/kg i.g.) co-administered with (L-NNA (20 mg/kg i.p.) with or without L-arginine (200 mg/kg i.g.), a substrate for NO-synthase; 5) curcumin (50 mg/kg i.g.) administered in rats with intact or capsaicin-induced functional ablation of sensory nerve fibers, and 6) curcumin (50 mg/kg i.g.) administered with capsazepine (5 mg/kg i.g.), the antagonist of vanilloid TRPV1 receptor. The number of gastric lesions was determined by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique, the plasma gastrin concentrations were measured using the radioimmunoassay (RIA) and the expression of mRNA for tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in gastric mucosa was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Curcumin dose-dependently reduced the WRS-induced gastric lesions, the dose inhibiting these lesions by 50% being about 50 mg/kg. These effects of curcumin were accompanied by an increase in GBF and the reduction in basal and histamine- or pentagastrin-stimulated gastric acid secretion. The protective and hyperemic activities of curcumin (50 mg/kg i.g.) against WRS lesions were significantly attenuated (P < 0.0

Topics: Animals; Anti-Ulcer Agents; Capsaicin; Curcumin; Cyclooxygenase 2; Female; Gastric Acid; Gastric Mucosa; Gastrins; Immersion; Male; Nitric Oxide Synthase Type II; Rats, Wistar; Restraint, Physical; RNA, Messenger; Stomach Ulcer; Stress, Psychological; TRPV Cation Channels; Tumor Necrosis Factor-alpha; Water

The present study was designed to verify whether frutalin (FTL) affords gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 ml of ethanol (96%). Mice in groups were pretreated with FTL (0.25, 0.5 and 1 mg/kg; i.p.), cimetidine (100 mg/kg; p.o.), or vehicle (0.9% of NaCl, 10 mL/kg; p.o.), 30 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm²) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide, sulphydryls, ATP-sensitive potassium channels, adrenoceptors, opioid receptors and calcium channels were analyzed. Treatments effects on ethanol-associated oxidative stress markers GSH and MDA were measured in gastric tissue. FTL afforded a dose-unrelated gastroprotection against the ethanol damage. However, it failed to prevent the ethanol-induced changes in the levels of GSH and MDA. It was observed that the gastroprotection by FTL was greatly reduced in animals pretreated with capsazepine, indomethacin, L-NAME or glibenclamide. Considering the results, it is suggested that the FTL could probably be a good therapeutic agent for the development of new medicine for the treatment of gastric ulcer.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Biomarkers; Capsaicin; Cimetidine; Ethanol; Galactose; Galectins; Gastric Mucosa; Glutathione; Glyburide; Indomethacin; Male; Malondialdehyde; Mice; Mice, Inbred Strains; NG-Nitroarginine Methyl Ester; Oxidative Stress; Phytotherapy; Plant Extracts; Stomach Ulcer

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.

Topics: Anacardic Acids; Anacardium; Animals; Anti-Ulcer Agents; Antioxidants; Capsaicin; Catalase; Ethanol; Gastric Mucosa; KATP Channels; Male; Malondialdehyde; Mice; Nitric Oxide; Prostaglandins; Rats; Rats, Wistar; Stomach Ulcer; Superoxide Dismutase

Validate the popular use of Plectranthus grandis in gastric disorders through the active components.. Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action.. Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances.. Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments.. The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.

Topics: Acetylcysteine; Animals; Anti-Ulcer Agents; Antioxidants; Capsaicin; Disease Models, Animal; Diterpenes; Ethanol; Gastric Mucosa; Glyburide; Indomethacin; Male; Mice; Mucus; NG-Nitroarginine Methyl Ester; Phytotherapy; Plant Extracts; Plant Leaves; Plectranthus; Quinones; Stomach; Stomach Ulcer; Sulfhydryl Compounds; Thiobarbiturates

The effect of Quebrachitol (2-O-methyl-L-inositol), a bioactive component from Magonia glabrata fruit extract was investigated against gastric damage induced by absolute ethanol (96%, 0.2 ml/animal) and indomethacin (30 mg/kg, p.o.), in mice. Quebrachitol at oral doses of 12.5, 25, and 50mg/kg markedly attenuated the gastric lesions induced by ethanol to the extent of 69%, 64%, and 53% and against indomethacin by 55%, 59%, and 26%, respectively. While pretreatment with TRPV1 antagonist capsazepine (5mg/kg, i.p.) failed to block effectively the gastroprotective effect of quebrachitol (25mg/kg) against ethanol damage, the non-selective cyclooxygenase inhibitor indomethacin (10mg/kg, p.o.), almost abolished it. Furthermore, quebrachitol effect was significantly reduced in mice pretreated with L-NAME, or glibenclamide, the respective inhibitors of nitric oxide synthase and K(+)(ATP) channel activation. Thus we provide the first evidence that quebrachitol reduces the gastric damage induced by ethanol and indomethacin, at least in part, by mechanisms that involve endogenous prostaglandins, nitric oxide release, and or the activation of K(+)(ATP) channels.

Topics: Animals; Arginine; Capsaicin; Diazoxide; Dose-Response Relationship, Drug; Ethanol; Glyburide; Indomethacin; Inositol; KATP Channels; Male; Mice; Misoprostol; Molecular Structure; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phytotherapy; Prostaglandins; Stomach Ulcer

Acid back-diffusion activates capsaicin-sensitive sensory neurons (CSN), leading to gastric hyperemic response. We examined the role of vanilloid type-1 receptor (VR1) in gastric hyperemic and ulcerogenic responses in rat stomach following exposure to taurocholate (TC).. Under urethane anesthesia, a rat stomach was mounted on an ex-vivo chamber, perfused with 50 mM HCl, and changes in PD, gastric mucosal blood flow (GMBF), and luminal acid loss were measured before and after exposure to 20 mM TC for 30 min, in presence of omeprazole. Capsazepine was co-applied with TC for 30 min to the stomach, while ruthenium red was given i.v. 10 min before TC treatment.. TC caused a marked PD reduction, followed by an increase of acid loss and GMBF, resulting in minimal damage in the mucosa. Chemical ablation of CSN attenuated the GMBF response to TC without affecting PD reduction and acid loss, and resulted in severe lesions, while none of these responses induced by TC was significantly affected by either capsazepine or ruthenium red. Intragastric capsaicin increased GMBF, and this response was attenuated by both capsazepine and ruthenium red as well as sensory deafferentation.. Both acid back-diffusion and capsaicin increase GMBF mediated by CSN, yet their modes of action differ in terms of capsazepine- or ruthenium red-sensitivity. Although the luminal H+ plays a modulator role for the physiological response mediated by CSN in the stomach, it is unlikely that the action results from the interaction of H+ with the capsazepine- or ruthenium red-sensitive site of VR1.

Topics: Animals; Capsaicin; Diffusion; Gastric Acid; Gastric Mucosa; Hydrogen; Male; Rats; Rats, Sprague-Dawley; Receptors, Drug; Ruthenium Red; Stomach; Stomach Ulcer; Taurocholic Acid; Time Factors; TRPV Cation Channels