Acid-induced Gastric Ulcers In Rats Research Articles

Protective effect of evodiamine on acetic acid-induced gastric ulcers in rats through regulation of ROS/ICAM1/Nrf2 signaling pathway

Purpose: To study the effect of evodiamine on the signaling pathway of ROS/ICAM-1/Nrf2 in rats with acetic acid-induced stomach ulcers. Methods: The rats were randomly assigned to five groups containing 10 rats each. Prior to acetic acidinduction of gastric ulcers, omeprazole (4.0 mg/kg/day), low-dose evodiamine (L-EVD, 20 mg/kg/day), and high-dose evodiamine (H-EVD, 40 mg/kg/day) were orally administered to the respective groups for 15 days. Following ulcer induction, the same treatments continued for an additional 7 days, for a total treatment duration of 22 days. The control (0.9 % saline) and acetic acid (model) groups were administered 0.9 % sodium chloride solution (10 mL/kg) for the same period. Thereafter, oxidative stress, inflammatory markers, macroscopic and microscopic evaluations were conducted on the gastric mucosa. Results: The acetic acid group showed significantly higher levels of oxidative and inflammatory markers, as well as damage and degeneration of the gastric mucosa when compared to control group (p < 0.05). However, both low-dose and high-dose evodiamine treatment groups demonstrated significant gastric healing. Administration of low-dose and high-dose evodiamine resulted in significantly lower levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO) and intracellular adhesion molecule-1 (ICAM-1, p < 0.05). Furthermore, evodiamine treatment led to significantly increased levels of glutathione (GSH) and nuclear facterythroid factor 2 (Nrf2). Conclusion: Evodiamine reduces oxidative stress, suppresses inflammatory reactions, and exerts an anti-ulcer effect on acetic acid-induced gastric ulcers in rats by modulating ROS/ ICAM-1/Nrf2 signaling pathway. More studies into the integration of evodiamine into conventional pharmaceutical treatments for gastric ulcers should be conducted.

Protective effect of evodiamine on acetic acid-induced gastric ulcers in rats through regulation of ROS/ICAM1/Nrf2 signaling pathway

Purpose: To investigate the anti-inflammatory and antiprotozoal effects as well as chemical profile of ethanol extracts of Hedyotis diffusa (Rubiaceae) (HDE) and Scutellaria barbata (Lamiaceae) (SBE). Methods: Dried whole plants collected in Vietnam were extracted with ethanol (30 and 96 %) by maceration for 4 weeks. The resulting extracts obtained after evaporating the solvent were stored in a refrigerator at 4 oC. Mouse carrageenan-induced inflammation and mouse macrophage cell line RAW264.7 were used to assess the in vivo and in vitro anti-inflammatory activities, respectively, while ciliate, Tetrahymena pyriformis was used to determine antiprotozoal effects. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was employed to analyze the chemical profiles of the extracts. Results: All the extracts manifested anti-inflammatory effects in vitro and in vivo. The HDE exhibited significantly higher in vitro anti-inflammatory activity than SBE (p < 0.05). Furthermore, in vivo antiinflammatory activity was higher in SBE compared to HDE. Both extracts exhibited antiprotozoal effects. The 96 % ethanol extract of both plants were more active than the 30 % ethanol extracts. Analysis by UHPLC‐Q‐TOF- MS revealed the presence of chrysin, apigenin and apigenin derivatives, naringenin, wogonin, quercetin and quercetin derivatives, as well as scutellarin. Conclusion: The HDE and SBE extracts from Vietnam exhibit significant in vivo and in vitro antiinflammatory activities and in addition, antiprotozoal activity against Tetrahymena pyriformis. These plants, therefore, are potential sources of antiprotozoal agents.

Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats

BACKGROUND Atractylodes japonica Koidz. ex Kitam. (A. japonica , Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it’s often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1β, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats

Ethnopharmacological relevanceQing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined. Aim of the studyThe present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism. Materials and methodsThe Wistar male rats (7 weeks old; weight 180–200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease. ResultsQWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats. ConclusionQWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.

Pharmacokinetics and anti-ulcerogenic effects of Zuojin gastric floating bio-adhesive pellets in rats with acetic acid-induced gastric ulcer

Introduction: Zuojin pills(ZP) have been shown to be effective in the treatment of gastric ulcer (GU); however, the efficacy of Zuojin gastric floating bio-adhesive pellets(ZFP) in GU treatment is yet to be evaluated. Methods: The pharmacokinetics(PK) and protective effects of ZFP against acetic acid-induced GU was examined using rat models. Mass spectrometry(MS) analysis was performed using a TSQ LC-MS system. A total of 50male Sprague-Dawley(SD) rats were randomly assigned to five groups: normal, acetic acid-induced, positive control (rabeprazole, 2 mg/kg/day), ZP (500 mg/kg/day), and ZFP (500 mg/kg/day) groups, to elucidate the anti-ulcerogenic effect of ZFP. Results: ZFP prolonged the residence time of the drug (MRT, 10.88 ± 0.93 h; T1/2, 42.83 ± 2.56 h) in rats and promote the effective absorption of the drug with obvious sustained-release properties. Compared with the control group, ZFP treatment for 7 d significantly increased the weight of the rats, significantly reduced ulcer index, increased gastric tissue Superoxide dismutase(SOD) activity, reduced gastric tissue Malondialdehyde(MDA) content, and increased serum IgA, IgM, IgG, and Interleukin-2(IL-2) levels. Additionally, histopathological analysis showed that ZFP treatment reduced inflammatory cell infiltration to mainly the mucosal layer, anda small amount of fibrous scar proliferative repair was observed in the mucosal defect area and the underlying inflammatory granulation tissue. Conclusion: These results indicated that ZFP prolonged the residence time of the drug in rats with sustained-release properties and had an obvious protective effect against acetic acid-induced GU in rats.

Acacetin Ameliorates Acetylsalicylic Acid-Induced Gastric Ulcer in Rats by Interfering with Oxidative Stress, Inflammation, and Apoptosis

Acacetin Ameliorates Acetylsalicylic Acid-Induced Gastric Ulcer in Rats by Interfering with Oxidative Stress, Inflammation, and Apoptosis

Mechanism of Saikosaponins from Radix bupleuri in the Treatment of Acetic Acid-Induced Gastric Ulcer in Rats

Mechanism of Saikosaponins from Radix bupleuri in the Treatment of Acetic Acid-Induced Gastric Ulcer in Rats

Gastroprotective activity of polysaccharide from the fruiting body of Hericium erinaceus against acetic acid-induced gastric ulcer in rats and structure of one bioactive fraction

This study aimed at investigating gastroprotective activity of Hericium erinaceus polysaccharide (HEP) and characterizing one of its bioactive fractions. Acetic acid-induced gastric ulcer (GU) rat model was used to evaluate the gastroprotective activity of HEP, while H2O2-induced injury GES-1 cell model was conducted to screen the bioactive fractions from HEP. Moreover, one of the bioactive fractions was characterized using methylation and 1D/2D NMR analysis. Results indicated HEP treatment could ameliorate acetic acid-induced GU in rats. HEP supplement decreased levels of interleukin-6, tumor necrosis factor-α and malondialdehyde and myeloperoxidase activity, and increased releases of nitric oxide, prostaglandin E2, epidermal growth factor, vascular endothelial growth factor and basic fibroblast growth factor and superoxide dismutase activity in gastric tissues of ulcerated rats. Five purified polysaccharides from HEP were screened to be bioactive fractions with cytoprotection on H2O2-induced injury in GES-1 cells. Among them, RP-S was characterized to be a (1 → 6)-β-D-glucan, whose backbone was composed of →6)-β-D-Glcp-(1 → residue and branched with T-β-D-Glcp-(1 → residue at O-3 position. In conclusion, HEP possessed gastroprotection against acetic acid-induced GU in rats and one of its bioactive fractions was a β-D-glucan. This study supports the utilization of HEP in anti-GU and provides evidences for the structure of gastroprotective HEP.

Evaluation of Therapeutic Efficacy of Stigma and Petal Extracts of Crocus sativus L. on Acetic Acid-Induced Gastric Ulcer in Rats

Saffron (Crocus sativus L.) has long been considered a medicinal plant in Traditional Persian Medicine (TPM) due to its therapeutic properties. Despite this interest, its effects on gastrointestinal disorders have not been completely taken into consideration. Hence, this study aimed to evaluate the pharmacological activity of ethanolic extracts of saffron stigma (SS) and saffron petal (SP) in acetic acid-induced gastric ulcer in rats. The gastric ulcer model was imitated by the serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed with 100 mg/kg and 200 mg/kg of ethanolic extracts of SS or SP, omeprazole (40 mg/kg), or saline for 12 days. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. The highest anti-ulcer activity was observed in the omeprazole-treated animals with the lowest ulcer size (4.29 ± 1.78 mm2). SS could not reduce gastric ulcer size in rats. Compared to the untreated rats, SP treatment significantly decreased ulcer indices in a dose-dependent manner. The gastric levels of PGE2, VEGF, and MDA were significantly elevated in the untreated animals with gastric ulcers compared to rats in the control group. The SS extract suppressed the elevated PGE2 and VEGF levels at both doses, while SP did not have a significant influence. Both SS and SP treatments significantly ameliorated MDA levels in rats with gastric ulcers. Omeprazole treatment enhanced the PGE2 level and suppressed MDA contents, but it did not influence the VEGF level. In conclusion, our findings demonstrated that the saffron stigma has no significant effects on the gastric ulcer healing process, while its petals accelerate the process. This discrepancy can be attributed to the difference in the main secondary metabolites between saffron stigma and petals.

Taxifolin and gastro-adhesive microparticles containing taxifolin promotes gastric healing in vivo, inhibits Helicobacter pylori in vitro and proton pump reversibly in silico

Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H+/K+-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm2). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H+/K+-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 μg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H+/K+-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.

Cenostigma macrophyllum Tul. var. acuminata Teles Freire Fraction Leaves Stimulate Gastric Healing in Rats and Human Cell Cultures.

Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae-Caesalpinioideae) is a medicinal plant traditionally used for treatment of gastric ulcer. This study evaluated the ulcer-healing activity of the hydroalcoholic fraction of C. macrophyllum Tul. var. acuminata Teles Freire leaves (Cm-FHA) and the tea of the leaves of C. macrophyllum (Cm-tea), as well as the possible action of Cm-FHA, through in vitro models. Leaves of C. macrophyllum were dried and powdered to obtain the Cm-FHA. Subsequently, the Cm-FHA was characterized phytochemically and biologically. Besides, Cm-tea was prepared. The gastric healing effects of Cm-tea and Cm-FHA were analyzed using the model of acetic acid-induced gastric ulcer in rats. The human gastric adenocarcinoma (AGS) cell line was employed as an in vitro model. Cm-tea promoted a protective effect against gastric ulcers induced by absolute ethanol. Cm-FHA or Cm-tea (100 mg/kg/7 days) exhibited a significant healing effect on ulcers induced by acetic acid. In the histological analysis, gastric mucosa treated with Cm-FHA or Cm-tea advanced restoration of the mucosal epithelium. In vitro, lower concentrations of Cm-FHA stimulated cell proliferation in the BrdU assay and cell migration. Cm-tea and Cm-FHA present a significant gastric healing effect in in vivo and in vitro models.

Immunohistochemical Studies of Age-Related Changes in Cell Proliferation and Angiogenesis during the Healing of Acetic Acid-Induced Gastric Ulcers in Rats.

Cell proliferation and angiogenesis are of utmost importance for healing to take place. The KI67 and EGFR proteins are markers of cell proliferation, while CD31 and factor VIII are markers of angiogenesis. To elucidate the mechanism responsible for delayed healing of the gastric injury in old age, we analyzed the expression of these markers in rats of different months during the healing of an acetic acid-induced gastric ulcer. Male Wistar rats (aged 3, 6, 12, and 18 months) divided into four groups, according to their ages, formed the experimental animals. Stomach tissue samples were collected on days 3, 7, 14, and 21 after induction for assessment of ulcer healing. The area of gastric mucosa healed was inversely proportional to age. The expression of markers of proliferation (KI67 and EGFR) and angiogenesis (factor VIII and CD31) decreased significantly (p < 0.05) in older rats when compared with younger ones (3 months > six months > 12 months > 18 months) on days 7, 14, and 21 after induction of gastric ulcer. This study revealed that the slower gastric ulcer healing rate in older rats might be due to reduced epithelial cell proliferation and angiogenic activities.

Protective Effect of Ocotillol, the Derivate of Ocotillol-Type Saponins in Panax Genus, against Acetic Acid-Induced Gastric Ulcer in Rats Based on Untargeted Metabolomics.

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.

Comparative Study of Najia and Nazi Acupunctures to Reduce Rat Gastric Ulcer

Gastric ulcer is a common digestive system disease, which leads to the serious decline in the life quality and effective therapies are in urgent need. Midnightmidday ebb flow acupunctures including Najia and Nazi acupunctures have been applied in clinics in China for more than one thousand years and the acupoints are selected according to the time rhythm. Najia acupuncture, namely day-prescription of acupoints, divides ten days (one cycle) into 120 two-hour periods and each period is coordinated with a meridian. Meanwhile, Nazi acupuncture, namely hour-prescription of acupoints, divides a day(one cycle) into 12 two-hour periods and each period is coordinated with a meridian. When there is a disease in a certain meridian, the relevant acupoints are operated in the corresponding time. However, the comparative efficacies of Najia and Nazi acupunctures on promoting the healing of gastric ulcer are still unknown. In this study, gastric ulcer rats were induced by acetic acid and were randomly divided into four groups: non-acupuncture group, normal acupuncture group, Najia acupuncture group and Nazi acupuncture group. After different treatments for continuous 10 days, the gained weight, gastric ulcer area and the thickness of gastric mucosa were measured and analyzed. Decreased ulcer area, increased mucosa thickness and dense scar tissue occurred in the Najia group and Nazi group compared to that in the non-acupuncture group (P&lt;0.05). However, there were no significant differences between Najia and Nazi acupuncture groups (P&gt;0.05). Thickness of gastric mucosa in Nazi acupuncture group increased significantly compared to normal acupuncture group (P&lt;0.05). Therefore, the findings in this study indicated that Najia and Nazi acupunctures had gastroprotective effects and accelerated the healing of acetic acid-induced gastric ulcer in rats, but no significant differences between them. It may provide valuable information for development of acupuncture for the treatment of gastric ulcer in clinics.

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.

ANTIOXIDANT AND ANTIULCER ACTIVITY OF ABRUS PRECATORIUS LEAF EXTRACT AGAINST ACETIC ACID-INDUCED GASTRIC ULCER IN RATS

Objective: The present study deals with the study of antiulcer activity of Abrus precatorius leaf extract in acetic acid-induced gastric ulcers was studied in rats.&#x0D; Methods: In the present study, A. precatorius leaf extract was carried out in antiulcer activity against acetic acid-induced gastric ulcer in rats. A. precatorius at doses of 150 mg/kg and 300 mg/kg were administered orally once daily for 10 days.&#x0D; Results: It was found that extract significantly reduced ulcer index. The plant leaves made gastric anti-secretory effect by decreasing gastric volume and acidity. Then, gastric mucin was increased, which showed gastric cytoprotective effect. The plant showed the prevention effect of increased lipid peroxidation during ulceration by acetic acid. Activities of the antioxidant enzymes were enhanced during ulceration by this plant leaves.&#x0D; Conclusion: Leaves of A. precatorius Linn. could decrease acetic acid-induced gastric ulcers in rats and this antiulcerogenic activity was mediated through antioxidant defense mechanism.

(−)-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.

Treatment Effects of Jinlingzi Powder and Its Extractive Components on Gastric Ulcer Induced by Acetic Acid in Rats.

Jinlingzi powder comprises Melia toosendan Sieb. et Zucc. and Corydalis yanhusuo (Y.H. Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu and is usually applied in clinic as traditional Chinese medicine for pain. The present study aims to investigate the therapeutic actions of Jinlingzi powder and its extracted components and theirs treatment mechanism on the acetic acid induced-gastric ulcer in rats. The gastric ulcer model was induced by the administration of acetic acid in rats (84 male). Jinlingzi powder water decoction, its polysaccharide, and nonalkaloid and alkaloid components were used to investigate the therapeutic actions on the acetic acid induced-gastric ulcer by measuring the related pharmacy and pharmacodynamic factors, including ulcer index, ulcer area, ulcer healing rate, interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), neurotensin (NT), platelet activating factor (PAF), thromboxane B2 (TXB2), and vascular endothelial growth factor (VEGF) in rat serum, acetylcholinesterase (AChE) in brain tissue, prostaglandin E2 (PGE2), and basic fibroblast growth factor (bFGF) in gastric tissue. Among the various groups, Jinlingzi powder and the nonalkaloid components caused significant changes in IL-8, TNF-α, NT, PAF TXB2, and VEGF values in the serum. The AChE content in the rats' brain tissue was also reduced after using Jinlingzi powder and the nonalkaloid components. Additionally, Jinlingzi powder and the nonalkaloid components considerably affect the amount of PGE2 and bFGF in a rat's stomach tissue. Therefore, Jinlingzi powder and the nonalkaloid components can effectively inhibit neutral neutrophil activation, prevent capillaries thrombosis, and protect gastric mucosa. Thus, the nonalkaloid components of the Jinlingzi powder play a key role in the treatment of gastric ulcer.

Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve

This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy. Whole-cell patch clamp recording showed that SNP depolarized the resting membrane potential of NG neurons, and enhanced capsaicin-induced inward current, which were both blocked by N-ethylmaleimide. Our results suggest that NO donor SNP alleviates acetic acid-induced gastric ulcer in rats via vagus nerve, while S-nitrosylation of TRPV1 may participate in this route. Our findings reveal a new mechanism for vagal afferent activation, and a new potential anti-inflammatory target.

Gastroprotective effect of palmatine against acetic acid-induced gastric ulcers in rats.

Gastric ulcers are one of the most common gastrointestinal disorders. The aim of this study was to investigate the gastroprotective activity and possible underlying mechanisms of palmatine against acetic acid-induced gastric ulcers in rats. Palmatine was administered orally for 7 consecutive days to treat ulcers. The ulcer area, ulcer inhibition rate, histological section, platelet-activating factor (PAF) level in serum, prostaglandin E2 (PGE2) level in gastric tissue, 5-hydroxytryptamine (5-HT) level in the brain and norepinephrine (NE) level in the adrenal glands were analyzed. Histological results showed that the ulcer areas were significantly decreased by both doses of palmatine (10 and 20 mg/kg/day) compared with the model group, and the ulcer inhibition rates were 51.42% and 60.92%, respectively. Palmatine treatment markedly increased the level of PGE2 and decreased PAF, compared with the model group; however, it had no significant effect on 5-HT and NE levels. The results indicated that palmatine may exert a gastroprotective effect against gastric ulcers, and the mechanisms might be associated with the anti-inflammatory status and the protection of gastric mucosa via increasing PGE2 and decreasing PAF rather than neurohumoral regulation through 5-HT and NE. Thus, palmatine is a potential drug for treatment of gastric ulcers.