Gastric Ulcer Healing Research Articles

Comparative study of effect of ranitidine and sitagliptin on healing of acetic acid induced gastric ulcer in rats

Gastric ulcer healing is a complex process that is regulated by several promoting factors including Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS). Diabetes mellitus is usually associated with delayed gastric ulcer healing. Hence, the current study was designed to compare the effect of sitagliptin (dipeptidyl peptidase-4 inhibitor) with ranitidine on gastric ulcer healing. The present study was conducted on 40 male albino rats that were divided into four equal groups: Group 1: normal control group, group 2: gastric ulcer model, Group 3: sitagliptin treated group, Group 4: ranitidine treated group. Rats were sacrificed ten days after ulcer induction and stomach was removed for histopathological examination and Immuno histochemical evaluation of COX-2 and iNOS. This study revealed that gastric ulcer healing was significantly impaired in the sitagliptin-treated group when compared with ranitidine treated group, evidenced by histopathological examination of stomach showing significantly larger ulcerated area and ulcer base maturation impairment.COX-2 and iNOS expression as well as mean vascular density (MVD) were significantly diminished in the sitagliptin-treated group as compared to ulcer model group as well as ranitidine treated group. A significant positive correlation was found between COX-2 and iNOS implying their synergistic action. A significant positive correlation was found between MVD on one hand and COX-2 and iNOS on the other hand pointing to their proangiogenic effect. This results raise the question of whether sitagliptin is advisable in diabetic patients with pre-existing gastric ulcer. Our preliminary experimental findings need to be substantiated by future human studies.

Human-like collagen promotes the healing of acetic acid-induced gastric ulcers in rats by regulating NOS and growth factors.

Human-like collagen (HLC), the collagen produced using fermentation technology, has been demonstrated previously to promote wound healing. However, the healing property of HLC in gastric ulcers remains to be verified. In this study, we investigated the healing efficacy and healing mechanisms of HLC on gastric ulcers. To investigate whether HLC still has healing activity on gastric ulcers after gastric digestion, we simulated gastric digestion in vitro to obtain a human-like collagen digestion product (HLCP) and used it as the control drug. A chronic gastric ulcer model induced by 60% acetic acid in rats was used to evaluate the healing effect of gastric ulcers in this study. The results showed that oral administration of HLC or HLCP for 4 or 7 days promoted ulcer healing, which can be directly observed by significant reductions in ulcer area. The oral administration of HLC and HLCP significantly increased the protein expression of growth factors (EGF, HGF, VEGF, bFGF and TGF-β1) and the HGF receptor (HGFr), promoted collagen deposition, regulated the activity of NOS, and decreased pro-inflammatory cytokines (TNF-a, il-6, il-10) and endothelin-1 (ET-1) levels in gastric tissue. Moreover, cell experiments showed that the effects of HLC on cell proliferation and migration are mainly caused by its digestion products. These findings indicate that HLC may be used as a nutritional supplement or therapeutic drug to promote the healing of gastric ulcers.

Manufacture and Assessment of the absorption capability of famotidine to 3D-nano-cellulose network

Background: Famotidine is one of gastrointestinal drugs which is used by drink or injection, soluble in acids and weakly dissolved in water. It has the effect of reducing gastric secretion by inhibiting histamine at the H2 receptor in the gastric mucosa wall, decreasing the secretion of HCl in gastric juice, the healing of gastric ulcers. Manufacture, In vitro Characterization And In vivo Bioavailability Evaluation of famotidine Loaded 3D-Nano-Cellulose Network (3DNC) by bacteria and Used for Oral Administration. Methods: Famotidine is a gastrointestinal H2-receptor antagonist drug with low bioavailability (40-45%). 3DNC can be produced from bacteria living in fermented green tea and is the material containing nano-sized fibers which is capable of loading Famotidine to form a prolonged release therapy to improve drug bioavailability. Results: This research has been produced 3DNC materials from bacteria in some nutrient media; it has used scanning electron microscope (SEM) to determine the 3DNC structure, spectrophotometer FT-IR to determine drug interaction to 3DNC, high performance liquid chromatography (HPLC) to determine Famotidine in rabbit plasma. Conclusion: Three-dimensional nano-cellulose network has an involvement of the nano-sized cellulose fibers with three dimensional networks that are capable of loading Famotidine drug. How to Cite this Article Pubmed Style Mai VH, Nguyen XT, Lai PL, Do TL, Le TP. and Assessment of the absorption capability of famotidine to 3D-nano-cellulose SRP. 2020; 11(7): 309-313. doi:10.31838/srp.2020.7.48 Web Style Mai VH, Nguyen XT, Lai PL, Do TL, Le TP. and Assessment of the absorption capability of famotidine to 3D-nano-cellulose http://www.sysrevpharm.org/?mno=127504 [Access: March 29, 2021]. doi:10.31838/srp.2020.7.48 AMA (American Medical Association) Style Mai VH, Nguyen XT, Lai PL, Do TL, Le TP. and Assessment of the absorption capability of famotidine to 3D-nano-cellulose SRP. 2020; 11(7): 309-313. doi:10.31838/srp.2020.7.48 Vancouver/ICMJE Style Mai VH, Nguyen XT, Lai PL, Do TL, Le TP. and Assessment of the absorption capability of famotidine to 3D-nano-cellulose SRP. (2020), [cited March 29, 2021]; 11(7): 309-313. doi:10.31838/srp.2020.7.48 Harvard Style Mai, V. H., Nguyen, . X. T., Lai, . P. L., Do, . T. L. & Le, . T. P. (2020) and Assessment of the absorption capability of famotidine to 3D-nano-cellulose SRP, 11 (7), 309-313. doi:10.31838/srp.2020.7.48 Turabian Style Mai, Van Hung, Xuan Thanh Nguyen, Phuong Lien Lai, Thuy Linh Do, and Thi Phuong Le. 2020. and Assessment of the absorption capability of famotidine to 3D-nano-cellulose Systematic Reviews in Pharmacy, 11 (7), 309-313. doi:10.31838/srp.2020.7.48 Chicago Style Mai, Van Hung, Xuan Thanh Nguyen, Phuong Lien Lai, Thuy Linh Do, and Thi Phuong Le. Manufacture and Assessment of the absorption capability of famotidine to 3D-nano-cellulose network. Systematic Reviews in Pharmacy 11 (2020), 309-313. doi:10.31838/srp.2020.7.48 MLA (The Modern Language Association) Style Mai, Van Hung, Xuan Thanh Nguyen, Phuong Lien Lai, Thuy Linh Do, and Thi Phuong Le. Manufacture and Assessment of the absorption capability of famotidine to 3D-nano-cellulose network. Systematic Reviews in Pharmacy 11.7 (2020), 309-313. Print. doi:10.31838/srp.2020.7.48 APA (American Psychological Association) Style Mai, V. H., Nguyen, . X. T., Lai, . P. L., Do, . T. L. & Le, . T. P. (2020) and Assessment of the absorption capability of famotidine to 3D-nano-cellulose Systematic Reviews in Pharmacy, 11 (7), 309-313. doi:10.31838/srp.2020.7.48

Gastric ulcer healing activity against acidified ethanol-induced gastric ulcer and gastroprotective mechanisms of Zingiber simaoense rhizome ethanol extract in rats

Background: Zingiber simaoense Y. Y. Qian (Zingiberaceae) rhizomes have been widely used to alleviate gastric disorders in Thai traditional medicine. Objectives: This study aimed to investigate the gastric ulcer healing activity of Z. simaoense rhizome ethanol extract (ZSE) against acidified ethanol-induced gastric ulcer and its possible gastroprotective mechanisms. Materials and Methods: The gastric ulcer healing activity of ZSE was evaluated using an acidified ethanol-induced gastric ulcer model in rats. The involvement of endogenous nitric oxide (NO) and sulfhydryl (SH) compounds in ZSE gastroprotection was also examined in addition to the determination of NO, malondialdehyde (MDA), and prostaglandin (PG) E2levels in rat gastric tissues as well as the determination of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and total phenolic content in ZSE. Results: ZSE at the dose of 240 mg/kg/day significantly accelerated gastric ulcer healing when observed on days 4 and 8 following ulcer induction. Pretreatment with either NG-nitro-L-arginine methyl ester or N-ethylmaleimide inhibited the gastroprotective activity of ZSE. Moreover, ZSE significantly increased NO and PGE2levels and decreased MDA levels in rat gastric tissues. DPPH radical scavenging activity and total phenolic compounds were also presented in ZSE. Conclusion: This study demonstrates the gastric ulcer healing activity of ZSE against acidified ethanol-induced gastric ulcer in rats. The possible gastroprotective mechanisms underlying the cytoprotective effect of ZSE might also involve gastric mucosal NO, SH compounds, and PGE2as well as its antioxidant activities.

Royal jelly accelerates healing of acetate induced gastric ulcers in male rats.

This study examined the healing potential of royal jelly on the acetic acid induced wounds healing in male rat's gastric mucosa. Scientific reports suggest that, bee products can help in the wounds healing. 96 adult male Wistar rats were divided into in 4 groups as follows: control, omeprazole 20 mg/kg, and royal jelly 50 and 200 mg/kg). Wound was induced in stomach mucosa of each rat with 100% acetic acid. Samples groups received omeprazole or royal jelly from 1st to 14th day after acetic ulcer induction. Gastric ulcer healing and histopathological parameters were evaluated on 4, 7, 10, 15th days after ulceration. Both descriptive and statistical analyses were used. P <0.05 was considered as significant. The royal jelly administration significantly reduced the depth of lesion in comparison with the control group (p<0.05) and attuned histopathological changes in the treatment groups. The largest healing effect was demonstrated with royal jelly on 10th treatment day, at a higher concentration (200 mg/kg). These findings supported that royal jelly had effectively contributed to the wound healing, valid gastroprotective activity, and can be used for peptic ulcer therapy.

Age-related changes in haematological parameters and biochemical markers of healing in the stomach of rats with acetic acid induced injury

This study examined the changes in haematological and biochemical variables in response to gastric mucosa injury in male Wistar rats divided into four groups according to their ages (3, 6, 12, and 18 months). 0.2 ml of acetic acid was injected intraluminal into the stomach glandular portion of each rat for 45 seconds under anaesthesia. Collection of blood and stomach samples occurred on days 3, 7, 14 and 21 post-induction of gastric ulcer. The results obtained from this study showed 100 % area of gastric mucosa healed in 3-month old rats, 91.72 %, 68.52 % and 62.81 % area of mucosa treated in 6, 12 and 18-month old rats respectively on day 21 post-induction of gastric ulcer. Increased circulation of blood cells in younger rats occurred, neutrophil-lymphocyte ratio (NLR) was decreased in younger rats (3 and 6 months) significantly (p < 0.05) when compared to older rats (12 and 18 months). Lipid peroxidation and glutathione (GSH) levels were elevated in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). In comparison, superoxide dismutase (SOD) and catalase levels were decreased in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). Histological evaluation showed evidence of early healing with re-epithelialisation and angiogenesis in younger rats, but older rats showed delayed healing. The study showed that the slower rate of healing of gastric ulcer with advancing age in rats might be due to reducing circulating blood cells and anti-inflammatory activities during healing via a lipid peroxidation-dependent mechanism.

Primary localized amyloidosis of the stomach mimicking healing gastric ulcer

Primary localized amyloidosis of the stomach mimicking healing gastric ulcer

Effectiveness of Opuntia ficus indica L. inermis Seed Oil in the Protection and the Healing of Experimentally Induced Gastric Mucosa Ulcer.

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from Opuntia ficus indica (OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm2), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H2-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.

Diet‐induced changes in gastric and faecal microbiota in horses: association with gastric ulcer healing

Diet‐induced changes in gastric and faecal microbiota in horses: association with gastric ulcer healing

A polysaccharide fraction from “ipê-roxo” (Handroanthus heptaphyllus) leaves with gastroprotective activity

A polysaccharide fraction from Handroanthus heptaphyllus leaves was obtained with a simple and quick purification method. Methylation analysis and NMR spectroscopy indicated the presence of a complex polysaccharide fraction mainly constituted by a type II arabinogalactan. This is the first report in literature on structural elucidation of polysaccharides of species from genus Handroanthus. Oral and intraperitoneal administration of the polysaccharide fraction from Handroanthus heptaphyllus (HHSF) protected the gastric mucosa in an acute model of gastric lesion induced by ethanol, preserving gastric mucus. Furthermore, in the indomethacin model, HHSF reduced wounded area and inhibited mucus and GSH depletion. HHSF also accelerated gastric ulcer healing, accompanied by the maintenance of GSH levels. In addition, in an oxidative stress model with human epithelial cell line (Caco-2), HHSF was able to preserve GSH levels and was not toxic to cells. Collectively, these results showed that HHSF has an interesting antiulcerogenic activity and could constitute an interesting option for the treatment of gastric ulcer.

Zinc l-carnosine in gastric ulcers: a profile of its use

Oral zinc l-carnosine (Gastrozin®) 75 mg twice daily is an effective gastric mucoprotective option for the treatment and prevention of gastric ulcers. The two components of the chelated compound (i.e. zinc and l-carnosine in a 1:1 ratio) provide beneficial anti-inflammatory, antioxidant and other effects that work together to support the natural mucoprotective mechanisms of the gastrointestinal tract. Zinc l-carnosine 75 mg twice daily has well established efficacy in the treatment of gastric ulcers, and is at least as effective as other mucoprotectants in this indication. It consistently provides rapid healing of gastric ulcers regardless of their underlying cause, such as gastritis, Helicobacter pylori infection and endoscopic submucosal dissection (ESD), or concurrent pharmacological treatment (e.g. H. pylori eradication or proton pump inhibitor therapy).

Angiotensin-(1-7) Enhances Mucosal Wound Healing in the Mouse Small Intestine

Purpose: Mucosal wound healing (WH) after injury due to necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) is important to ameliorate inflammation and restore normal intestinal function. Regulators of WH could include components of the angiotensin system such as the heptapeptide angiotensin-(1-7) (Ang-(1-7)). Administration of Ang-(1-7) decreases colitis and accelerates gastric ulcer healing in experimental rodent models; these effects are likely mediated via the MAS1 receptor (MAS1R). The purpose of this study is to determine if the Ang-(1-7)/MAS1R …

(−)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells

The gastroprotective property of (−)-myrtenol, a monoterpenoid, has been demonstrated previously against acute gastric ulceration induced by ethanol. However, the healing property of (−)-myrtenol in a chronic gastric ulcer model remains to be verified. This study evaluated its healing efficacy and the mechanism involved using the rat model of chronic gastric ulcer induced by serosal injection of 80% acetic acid in vivo, and human gastric adenocarcinoma cells (AGS) in vitro. The results showed that compared to vehicle-treated ulcer controls, oral administration of (−)-myrtenol (50 and 100 mg/kg/day) for 7 days promoted ulcer healing, as indicated by significant decreases in ulcer area and volume. The macroscopic and microscopic findings confirmed the healing potential of (−)-myrtenol. The ulcer healing activity was also associated with significant increases in gastric mucin content, collagen deposition, number of cells with positive marking for proliferating cell nuclear antigen (PCNA), and by changes in the expression of the inflammatory parameters tumor necrosis factor (TNF)-α, interleukin (IL)-1β and cyclooxygenase (COX)-2, as well as a decrease of metalloproteinases (MMP-9 and MMP-2) activity. Furthermore, in vitro assays using the AGS cultures revealed that (−)-myrtenol favors wound healing activity via stimulation of cell proliferation and migration without altering the cell viability. Taken together, these findings indicate that (−)-myrtenol has gastro-cytoprotective and ulcer healing properties that can be further explored to develop a new therapeutic agent from a natural source for the treatment of gastric ulcer.

Hydroalcoholic extract from Baccharis dracunculifolia recovers the gastric ulcerated tissue, and p-coumaric acid is a pivotal bioactive compound to this action.

Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.

Anti-inflammatory and wound healing effects of cream containing Curcuma mangga extract

Ethnopharmacological relevanceCurcuma mangga Valeton & Van Zijp. (Zingiberaceae family) contains curcuminoids and diterpenes which have anti-inflammatory effect. In traditional use, the elixir of this plant has been used to detoxify the poisonous plants, treatment of gastric ulcer, chest pain, fever, skin disease and womb healing. This plant has also been reported for anti-inflammation in carrageenan-induced rat paw edema. Aim of the studyThis study is aimed to evaluate the anti-inflammatory and wound healing effects of cream containing C. mangga in the formulation as well as physical and chemical stabilities. Materials and methodsThree cream base formulas were evaluated for color, smell, pH values, viscosity and separation. The most stable cream base was chosen to mix with 2–10% of C. mangga extract. After that, the physical, chemical and biological properties of C. mangga cream before and after heating-cooling were evaluated. ResultsThe results showed that C. mangga cream exhibited good consistency, a pH range of acid value (5.0–6.0) and the cream was stable. Cream containing 10% w/w C. mangga inhibited inflammation before and after accelerating conditions with IC50 values of 34.1 and 37.9 μg/ml which were better than 5% (IC50 = 42.9, 44.7 μg/ml) and 2% (IC50 = 49.1, 49.6 μg/ml), respectively. In addition, the anti-inflammatory effect of cream containing C. mangga was found to be better than diclofenac gel (IC50 = 54.3 μg/ml). Cream containing C. mangga before and after heating-cooling test at 1 and 3 μg/ml enhanced HDF viability of over 100%, while cream containing 5% w/w C. mangga before and after heating-cooling test enhanced migration of HDF cells at 36 h up to 75–80%. The curcuminoids which are curcumin, demethoxycurcumin and bisdemethoxycurcumin showed good chemical stability after heating-cooling test by using HPLC with the relative peak area % at 10:75:15, respectively. ConclusionThis study concluded that the development of cream containing C. mangga could reduce inflammation and heal the wound.

3445 Cannabis use and risk of H. pylori infection; analysis of inpatients and residents of the US.

OBJECTIVES/SPECIFIC AIMS: Cannabinoids suppress gastric acid secretion, ameliorate gastric inflammation, and promote gastric ulcer healing, all of which are triggered by H pylori (Hp). Our aim was to determine the relationship between cannabis use and: 1) H pylori infection (HPI) among community residents 2) clinical peptic ulcer disease (PUD) and its complications among hospitalized patients. METHODS/STUDY POPULATION: We performed case-control studies with records from the NHANES III (n=4,556) and HCUP-NIS 2014 (n=4,555,029), and respectively identified subjects with seropositivity for H pylori and clinical PUD, and their cannabis usage status. In the NHANES III, we estimated the adjusted prevalence rate ratio (aPRR) of having HPI with cannabis use, using generalized estimating equations. In the NIS, we propensity-matched cannabis users to non-users in ratio 1:1 (68,073:68,073) and measured the aPRR of having PUD and its complications (SAS 9.4). RESULTS/ANTICIPATED RESULTS: In NHANES III, associated with decreased HPI seropositivity were cannabis ever-users (aPRR: 0.79[0.66-0.95]), greater than 10 times lifetime usage (0.65[0.5-0.84]) and recent 31-day usage (0.67[0.48-0.98]), compared to never usage. In the HCUP-NIS, cannabis users had decreased risk for total PUD (aPRR: 0.74[0.61-0.89]), duodenal PUD (0.48[0.35-0.60]) and PUD complications including hemorrhage (0.58[0.37-0.90]), perforation (0.66[0.51-0.87]), but not obstruction (1.75[0.51-5.98]). DISCUSSION/SIGNIFICANCE OF IMPACT: Cannabis usage is related to a reduced likelihood of having HPI in the community and also mitigate against having complicated presentations to the hospital. More translational studies are needed to illuminate the details of this relationship, given the high worldwide prevalence of both cannabis use and HPI.

Can the gastric healing effect of Eugenia punicifolia be the same in male and female rats?

Ethnopharmacological relevanceEugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as “pedra-ume-caá,” is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol. Materials and methodsThe healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm2), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters. ResultsMacroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (p < 0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (p > 0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (p < 0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (p < 0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (p < 0.05). ConclusionThese findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences.

Time-dependent course of gastric ulcer healing and molecular markers profile modulated by increased gastric mucosal content of carbon monoxide released from its pharmacological donor

Background and purposeBesides hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways. Experimental approachWistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i.g. throughout 3, 6 or 14 days with vehicle or CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2, 2.5 mg/kg). Gross and microscopic alterations in gastric ulcer size and gastric blood flow (GBF) at ulcer margin were determined by planimetry, histology and laser flowmetry, respectively. Gastric mRNA/protein expressions of platelet derived growth factors (PDGFA-D), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGFA) and their receptors, heme oxygenases (HMOX), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX-2), hypoxia inducible factor (HIF)-1α, anti-inflammatory annexin-1 and transforming growth factor (TGF-β1) were assessed by real-time PCR or Western blot. TGF-β1-3 and IL-10 plasma concentration were measured using Luminex platform. Prostaglandin E2 content at ulcer margin was assessed by ELISA. Key resultsCORM-2 decreased ulcer area and increased GBF after 6 and 14 days of treatment comparing to vehicle. CO donor upregulated HGF, HGFr, VEGFR1, VEGFR2, TGF-β1, annexin-1 and maintained increased IGF-1, PDGFC and EGF expression at various time-intervals of ulcer healing. TGF-β3 and IL-10 plasma concentration were significantly increased after COMR-2 vs. vehicle. ConclusionsCO time-dependently accelerates gastric ulcer healing and raises GBF at ulcer margin by mechanism involving subsequent upregulation of anti-inflammatory, growth promoting and angiogenic factors response, not observed physiologically.

Cochlospermum regium (Mart. ex Schrank) Pilg.: Evaluation of chemical profile, gastroprotective activity and mechanism of action of hydroethanolic extract of its xylopodium in acute and chronic experimental models

Ethnopharmacological relevanceCochlospermum regium (Bixaceae) is a native shrub of Brazil and its xylopodium (infusion/decoction) is being used for the treatment of gastritis, ulcers, arthritis, intestinal infections, gynaecological infections, skin diseases, among others. The aim of the present study was to evaluate the gastroprotective/antiulcer activity and the mechanism of action of hydroethanolic extract of C. regium xylopodium (HECr), using in vitro and in vivo models. Additionally, phytochemical constituents were identified by high-performance liquid chromatography (HPLC). Materials and methodsC. regium xylopodium was macerated with ethanol/water to obtain the HECr. The phytochemical characterisation was carried out by HPLC. The antiulcer efficacy of HECr (25, 100 and 400 mg/kg, p.o.) was evaluated using acute acidified ethanol (HCl/EtOH), piroxicam and water immersion-induced experimental ulcer models. Chronic gastric ulcer healing activity of HECr was evaluated through acetic acid (99.8%) – induced model. Histological analysis and myeloperoxidase (MPO), glutathione (GSH), catalase (CAT) activities were also evaluated in chronic ulcer induced gastric tissues. The plausible mode of action of the HECr was assessed by estimation of gastric wall mucus production and the role of gastric secretion in pylorus ligature. The animals were also pre-treated with various inhibitors which includes indomethacin (10 mg/kg, p.o.) a selective inhibitor of cyclooxygenase, L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, glibenclamide, a ATP-sensitive potassium channels (K+ATP) blocker (5 mg/kg, p.o.) or yohimbine (2 mg/kg, i.p.), an α2-adrenergic receptor antagonist. In vitro, Helicobacter pylori action was done by broth microdilution method. ResultsThe HPLC analysis data revealed the presence of gallic acid, rutin, myricetin, morin and kaempferol. HECr promoted protective effect against acute ulcers induced by HCl/EtOH with inhibitions of 47.52% (p < 0.01) and 62.69% (p < 0.001) at 100 and 400 mg/kg, and in piroxicam by 34.11% (p < 0.05), 49.14% (p < 0.01) and 61.34% (p < 0.001), at 25, 100 or 400 mg/kg, respectively, and in water restraint stress by 78.26% inhibition, p < 0.001, at the dose of 400 mg/kg when compared to the vehicle control group respectively. In the chronic gastric ulcer model, HECr (25, 100 and 400 mg/kg p.o.) significantly (p < 0.001) decreased the injured area by 58.80%, 77.87% and 71.10% respectively. Histological examination indicated that oral treatment of HECr promoted healing of gastric lesions by regenerating gastric mucosa layer with less inflammatory cells. HECr augmented the GSH, CAT activities and reduced MPO level. The pre-treatment with HECr increased the gastric wall mucus production. It also significantly altered the gastric secretion parameters by causing the reduction in the gastric juice volume, elevated the pH level and reduced the total acidity at all doses tested when compared with the vehicle group. HECr at the most active dose (100 mg/kg) reversed completely the reduction of PGs, NO production, closure of K+ATP- channels and α2-adrenoreceptor blockage – induced damages. In microdilution assay, the HECr showed good anti-Helicobacter pylori effect with MIC = 100 µg/mL. ConclusionThe HECr presented preventive and curative effects in the experimental gastric ulcer models, besides good anti-Helicobacter pylori activity, which supports the traditional medicinal use of the xylopodium of this plant for gastrointestinal diseases. The underlying mechanisms of this antiulcerogenic/antiulcer action involve, at least, augmentation of mucus production, inhibition of gastric secretion, stimulation of PGs and NO synthesis. And that it involves activation of K+ATP channels and α-2-adrenergic receptors, in addition to an antioxidant activity, probably due to the presence of gallic acid and flavonoids in HECr.

Protective effect of licorice (glycyrrhiza glabra linn) on indomethacin-induced gastric ulcer in male albino rats.

Objective: This study aimed to investigate the protective role of licorice on indomethacin-induced gastric ulcer in male albino rats compared to anti-ulcer drug; ranitidine. Methods: Fifty male adult rats were randomly allocated into five groups (10 rats/each); control, licorice, indomethacin, licorice/indomethacin, and ranitidine/indomethacin treated groups. Serum, gastric juice, and gastric tissues were collected for biochemical and histopathological analysis. Results: The obtained results revealed that licorice pre-treatment showed potent anti-ulcerative effect as; volume and total acidity of gastric secretion were markedly decreased, attenuated the severity of gastric lesion as confirmed by PM and histopathological examination showed preservation of gastric epithelium and ulcer healing. Moreover, gastric ulcer score, gastric MDA, and serum IL-6 were obviously decreased along with increased gastric GSH, CAT activity and NO. Interestingly licorice had no side effects on the liver and kidney evidenced by increased serum total protein, and albumin besides declined the activities of serum aminotransferases without significant changes in the serum urea, uric acid, sodium, potassium, and chloride levels. Conclusion: It was concluded that the used dose of licorice showed potent anti-ulcerative activity and more safer on the liver and kidney functions compared to the standard commercial drug; ranitidine.