The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.
Animals ; Cytokines ; Gastric Mucosa ; Indomethacin ; Omeprazole ; pharmacology ; Phytochemicals ; pharmacology ; Random Allocation ; Rats ; Rosaceae ; chemistry ; Stomach Ulcer ; chemically induced ; drug therapy ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

OBJECTIVECarica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria. This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats.

METHODSThirty male rats were separated into 6 groups (A-F) of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle (distilled water), cimetidine 200 mg/kg body weight (BW), or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW (groups A, B, C, D, E and F, respectively). Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation.

RESULTSCarica papaya seed extract significantly (P< 0.05) increased gastric pH and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly (P< 0.05) decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups (D, E and F) were increased significantly over the group B (P< 0.05). Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract.

CONCLUSIONIn this study, pretreatment with aqueous extract of Carica papaya seed exhibited anti-ulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.

Animals ; Anti-Ulcer Agents ; administration & dosage ; Carica ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Duodenal Ulcer ; chemically induced ; diagnosis ; drug therapy ; Gastric Acidity Determination ; Indomethacin ; pharmacology ; Male ; Peptic Ulcer ; chemically induced ; diagnosis ; drug therapy ; Plant Extracts ; administration & dosage ; Rats ; Seeds ; Stomach Ulcer ; chemically induced ; diagnosis ; drug therapy ; Treatment Outcome

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Arachidonate 5-Lipoxygenase/drug effects ; Calcitonin Gene-Related Peptide/drug effects ; Cyclooxygenase 1/drug effects ; Cyclooxygenase 2/drug effects ; Disease Models, Animal ; Gastric Mucosa/chemistry/drug effects ; Group IV Phospholipases A2/drug effects ; Male ; Momordica/*chemistry ; Peroxidase/drug effects ; Plant Extracts/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Seeds/*chemistry ; Stomach Ulcer/chemically induced/*prevention & control ; Treatment Outcome

OBJECTIVETo observe the effects and mechanisms of Pongamia pinnata root flavonoids (PRF) on the experimental gastric ulcer induced by acetic acid and to study the mechanism of PRF on the quality of ulcer healing.

METHODSThe models were established by acetic acid erosion, the quality of ulcer healing of PRF on the model of gastric ulcer were observed. The contents of epidermal growth factor (EGF) in serum were determined by radioimmunoassay. The expression of EGF and transforming growth factor-alpha (TGF-alpha) were detected by immunohistochemistry (SP).

RESULTSPRF significantly inhibited ulcerative formation induced by acetic acid (P < 0.05, P < 0.01). PRF could significantly increase the EGF and TGF-alpha (P < 0.05, P < 0.01) expression of para-ulcer mucosa tissue and improve the EGF contents in blood serum (P < 0.05, P < 0.01).

CONCLUSIONPRF increases the contents of EGF in serum and the expression of EGF and TGF-alpha in the tissue around gastric ulcer which might be one of possible mechanisms that PRF improves quality of ulcer healing.

Acetic Acid ; Animals ; Epidermal Growth Factor ; blood ; Female ; Flavonoids ; pharmacology ; Gastric Mucosa ; metabolism ; Male ; Millettia ; chemistry ; Plant Roots ; chemistry ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; Transforming Growth Factor alpha ; metabolism

OBJECTIVETo investigate the effect of Jiangbaiweiyan tablet, a Chinese medicine compound composed of Alpinta Officinarum, Cyperus Rotundus, Bulbus Lilii and Rlindera Strychnifolia, on ethanol-induced gastric mucosa injury in rats.

METHODSAcute gastric ulcer was induced in rats with absolute ethyl alcohol. The ulcer index was used to evaluate the extent of the gastric mucosa injury.

RESULTSThe ulcer indexes of the model group, the mid-dose (1.08 g x kg(-1) x d-(-1)1) and high-dose (2.16 g x kg(-1) x d-(-1)) of Jiangbaiweiyan tablet groups were 141.58±47.43, 24.83±23.04 and 2.12±2.58, respectively (P<0.01).

CONCLUSIONJiangbaiweiyan tablet has protective effects on ethanol-induced gastric mucosa injury in rats, which may be related to anti-oxidation and enhancing tissue regeneration capacity.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Ethanol ; toxicity ; Female ; Gastric Mucosa ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; chemically induced ; pathology ; prevention & control ; Tablets

OBJECTIVETo examine the protective effects of wasp (Vespa magnifica) honeycomb extract (WCE) against gastric lesions in rats induced by 60% acidified ethanol, and evaluate its capacity to suppress oxidative stress in the gastric tissue.

METHODSWistar rats were subjected to intragastric administration of 60% acidified ethanol to induce gastric lesions following an 8-day oral pretreatment with WCE at 0, 25, 100 and 150 mg/kg or with saline. The levels of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, myeloperoxidase (MPO) activity and total antioxidant capacity in the gastric tissues were determined.

RESULTSOral administration of 25, 100 and 150 mg/kg WCE prior to 60% acidified ethanol administration significantly inhibited the formation of gastric lesions (with a reduction by 44.2%-87.1%), decreased the mucosal MPO activity (by 16.4%-56.6%) and increased the total antioxidant capacity of the gastric tissue (by 0.5, 1.47 and 1.83 folds, respectively) in a dose-dependent manner. At a high concentration (above 1 mg/ml), WCE also exhibited a stronger DPPH radical scavenging activity than butylated hydroxytoluene (BHT).

CONCLUSIONThe ethanol extract of wasp honeycombs can suppress the formation of acidified ethanol-induced gastric lesions by reducing free radical oxidation and neutrophils infiltration in the gastric tissue in rats.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Ethanol ; adverse effects ; Female ; Honey ; Male ; Materia Medica ; pharmacology ; therapeutic use ; Neutrophil Infiltration ; drug effects ; Oxidative Stress ; drug effects ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Stomach Ulcer ; chemically induced ; prevention & control ; Wasps ; chemistry

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 microg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.
Adolescent ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Double-Blind Method ; Duodenal Ulcer/chemically induced/*prevention & control ; Endoscopy, Gastrointestinal ; Female ; Gastric Mucosa/drug effects ; Humans ; Male ; Middle Aged ; Misoprostol/*adverse effects ; Plant Extracts/*adverse effects ; Stomach Ulcer/chemically induced/*prevention & control

OBJECTIVETo explore the differences of the main pharmacological action in wild and cultivated Atractylodes lancea.

METHODStudy the effect of the 70% ethanol extracts from the wild and the culticated A. lancea on the mice with gastriculcer induced by absolute ethyl alcohol or HCl. Stdudy the effect on intestinal propulsive function in mice by measuring the length of intestine and distance of Indian ink. Observe anti-bacteria effect in vitro of the A. lancea by determining the minimum inhibitory concentrations.

RESULTThe pharmacological action, which made a little difference in the sane productive places, and made significant differences in different productive places. Compared to Jurong, it has better actions in Luotian on small intestinal propulsive function and bacteriostatic action. There was not an obvious difference in protective effect on gastric ulcer induced by absolute ethyl alcohol and 0.6 mol x L(-1) HC1 between different locations.

CONCLUSIONTo the main effect, cultvated A. lancea had no significant difference on the whole but having better result in some respects, which can provide the pharmacodynamics evidence of cultivated A. lancea being used instead of the wild.

Animals ; Atractylodes ; chemistry ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Motility ; drug effects ; Humans ; Male ; Mice ; Stomach Ulcer ; chemically induced ; drug therapy ; pathology ; physiopathology