Stress-induced Gastric Ulcers Research Articles

The Results of Gastric pH-metry in Patients with Extensive Burns

Aim of studyTo study of the role of hydrochloric acid in the genesis of stress-induced gastric ulceration in patients with extensive burns.Material and methodsThe results of gastroscopy and endoscopic pH-metry of 30 young patients with extensive burns (19 male patients and 11 female patients). The acidity of the gastric contents was measured on day 1,7 and 14 after the trauma.ResultsIt was found that the early period of burn disease was followed by the pH growth in the acid-producing area of the stomach to 3.8–4.2 (p=0.002–0.020). This indicated that extensive burns provoked a significant decrease of hydrochloric acid production by parietal cells of the stomach. The restoration of the acid production occurred only 14 days after thermal injury and was not followed by the development of a hyperacid state. The frequency of erosive-ulcerative lesions detection in the gastric mucosa by the end of the first day after receiving burns was 83%, 87% on day 7, and 96% on day 14. In total, stress-induced lesions of the gastrointestinal mucosa were diagnosed in 26 of 30 patients with a shock-induced thermal injury. Consequently, in patients with burn shock the protective factors of the gastric mucosa were depressed so that a minimum amount of hydrochloric acid was sufficient to damage it.ConclusionInhibition of acidogenic function is typical for patients with burn disease. Hydrochloric acid does not play a leading role in the genesis of stressinduced ulceration in patients with severe thermal trauma.

Tocopherol and Tocotrienol: Therapeutic Potential in Animal Models of Stress.

Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation. The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress. This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism, are discussed.

Gastroprotective effect of the protease-rich extract from sheep abomasum against stress-induced gastric ulcers in rats

In this study, ultrasound-assisted extraction method (UAE) was developed to obtain the protease-rich extract from sheep abomasum (SAE). UAE parameters were first optimized using response surface methodology. Ultrasonic time of 18 min, ultrasonic power of 260 W, and a liquid/solid ratio of 22 mL/g resulted in the highest proteolytic activity and yield of the SAE (4,951.3 U/g, 14.3%, respectively). Then we investigated SAE's gastroprotective effect against gastric ulcers induced by water immersion-restraint stress in rats. After 7 days of intragastric administration of the SAE (0.2 g/kg/day), the ulcer index (2.710.97; p

Evidence for gastroprotective, anti-inflammatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats

The Cordia dichotoma (CD) is having anticancer and other pharmacological effects as it contains mainly flavonoids. The present study was aimed to demonstrate the gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD revealed the presence of bioflavonoids and determination of quercetin was confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg, 100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally was used as the reference standard. The various parameters like gastric volume, gastric pH, total acidity, ulcer index, percent protection were estimated for assessment of anti-secretory and gastroprotective effects of MECD. At the same time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10 were also estimated according to their respective method of estimation using analyzing kit. The MECD have reduced gastric volume, total acidity and gastric mucosal damage in both the experimental models significantly and dose dependently as compared with control group. Similarly the antioxidant enzymes like SOD and CAT were increased while MDA levels were decreased significantly, at the same time TNF-α and IL-6 levels were decreased and anti-inflammatory IL-10 levels were increased significantly in MECD treated groups. Thus the pretreatment with MECD has shown significant gastroprotective potential probably due to its antioxidant and anti-inflammatory properties.

Effect of allantoin on experimentally induced gastric ulcers: Pathways of gastroprotection

Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters of gastric acid secretion and attenuated both the vascular permeability and MPO activity. The levels of pro-inflammatory cytokines were also reduced, accompanied by a restoration of CAT activity and GSH levels. Notably, allantoin treatment preserved the gastric-adhered mucus and PGE2 levels after ethanol administration. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. In summary, we demonstrated for the first time that allantoin possesses gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory, and cytoprotective mechanisms. The antisecretory and cytoprotective mechanisms are probably associated with an increase in PGE2 levels.

English

Endopleura uchi (Huber) Cuatrec. (Humiriaceae), the Brazilian Amazon plant, is used in folk medicine to treat arthritis and gastric ulcer. Bergenin, one of the chemical constituents of E. uchi, has anti-inflammatory properties. Its acetylation results in acetylbergenin, which is extracted to investigate its potential anti-inflammatory and antiulcer properties using an assay for croton oil-induced ear edema, rat paw edema induced by carrageenan and dextran, carragenin-induced peritonitis, and stress-induced gastric ulcer. In ear erythema induced by croton oil, acetylbergenin presented a significant 75.60% inhibition (p<0.001). The oral administration of 6.8 mg/kg of acetylbergenin significantly inhibited the carrageenan-induced edema formation by 35.09% (p<0.05) and the dextran-induced edema by 33% (p<0.05). The migration of neutrophils toward the peritoneal cavity was inhibited in acetylbergenin (6.8 mg/kg) treated animals by 70% (p<0.01). In the stress-induced gastric ulcer, acetylbergenin inhibited 78.55% of gastric lesions. The results suggest that, the anti-inflammatory action of acetylbergenin appears to be dependent on cyclooxygenase (COX-2) inhibition. Furthermore, although the anti-inflammatory activity of acetylbergenin is a characteristic of nonsteroidal compounds, it causes little deleterious interference in the gastric mucosa. Key words: Endopleura uchi, bergenin, acetylbergenin, anti-inflammatory, antiulcerogenic activity.

Evaluation of a poly-herbal preparation for the treatment of peptic ulcer

The aim of this study was to validate the traditional uses of ulcerene, a poly-herbal formulation in ethanol, aspirin and stress-induced gastric ulcer model of rat. The extent of gastric ulcer formation was studied, using ulcer score, ulcer index, percentage cure through gross examination and histopathological evaluation. A significant (p<0.001) dose-dependent anti-ulcerant effect was observed in ulcerene (50 and 100 mg/kg)-treated group with highest effectiveness against ethanol-induced ulcer. The concentration-dependent spasmolytic effect was seen in spontaneously contracting, high K+ (80 mM) and carbachol (1 µM)-induced jejunum contractions (10, 0.3 and 1 mg/mL), similar to dicyclomine (10, 1 and 3 µM), indicated non-specific spasmolytic mechanism behind the effect. By considering these results, ulcerene can be suggested for the treatment of peptic ulcer.

In vivo effect of Piper sarmentosum methanolic extract on stress-induced gastric ulcers in rats.

IntroductionPiper sarmentosum (Piperaceae) is traditionally used by Asians to treat numerous common ailments including asthma, fever and gastritis. The aim of the research was to determine and compare the effects of Piper sarmentosum (PS) with omeprazole (OMZ) on gastric parameters in rats exposed to restraint stress.Material and methodsThe methanolic extract of PS was prepared in the dose of 500 mg/kg. Twenty-eight male Wistar rats were assigned to 4 equal sized groups: two control groups and two treated groups which were supplemented with either PS or OMZ orally at a dose of 500 mg/kg and 20 mg/kg body weight respectively. After 28 days of treatment, one control group, the PS and OMZ group were subjected to a single exposure of water-immersion restraint stress for 3.5 h. After the last exposure to stress, the stomach was excised for evaluation of the parameters.ResultsOral supplementation of PS was as effective in preventing the formation of gastric lesion when compared with OMZ (p < 0.05). The increased gastric acidity and MDA due to stress was also reduced with supplementation of PS and OMZ. Only PS had the ability to reduce prostaglandin E2 loss (p = 0.0067) and have the ability to down regulate cyclooxygenase-2 (COX-2) mRNA expression (p = 0.01) with stress exposure.ConclusionsPiper sarmentosum possesses a similar protective effect against stress-induced gastric lesions as omeprazole. The protective effect was associated with decreased lipid peroxidation, increased prostaglandin E2, reduction in gastric acidity and reduction in COX-2 mRNA expression which was altered by stress.

Effect of moxa-burning heat stimulating Liangmen (ST 21) and Zusanli (ST 36) on proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer

ObjectiveTo observe the effect of moxa-burning heat stimulating acupoints of Liangmen (ST 21) and Zusanli (ST 36) on the proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer. MethodsForty rats were randomly divided into four groups: negative control (NC), ulcer control (UC), acupoints of stomach meridian (ASM), and acupoints control (AC). The acute gastric ulcer model was established by bound and water immersion. Rats in NC and UC groups didn't receive any moxa-burning heat stimulating treatment, while rats in ASM and AC groups were treated with buringmoxa heat stimulating the acupoints of Liangmen (ST 21) and Zusanli (ST 36) and their controlled points, respectively. Rats in all groups were sacrificed after 12 consecutive days treatment. The ulcer index was evaluated by using Guth's method. The expression of tumor necrosis factor-alpha (TNF-α), apoptotic protease activating facter-1 (Apaf-1), Caspase-3, p21 activated kinase 1 (PAK1), extracellular regulated protein kinases 2 (ERK2), phosphorylated ERK2 (pERK2), phosphoinositide 3-kinase (PI3K) and RAC-alpha serine/threonine-protein kinase (Akt) in gastric mucosa was detected by enzyme linked immunosorbent assay (ELISA). ResultsCompared with UC group, the ulcer index of ASM and AC groups decreased, and the injured gastric mucosa was improved, the expression of TNF-α, Apaf-1 and Caspase-3 in gastric mucosa was significantly reduced (P < 0.05), while the expression of PAK1, ERK2, pERK2, PI3K and Akt in gastric mucosa was significantly increased (P < 0.05). And ASM showed better effect than AC group (P < 0.05). ConclusionMoxa-burning Heat stimulating of Liangmen (ST 21) and Zusanli (ST 36) could promote the recovery of gastric mucosal lesion probably by inhibiting cell apoptosis and promoting cell proliferation in stress-induced gastric ulcer.

The effect of simvastatin pretreatment on stress-induced gastric ulcer in rats

Amac: Bu calismada sicanlarda stres ile uyarilan mide ulserinde simvastatin’in (SIM) olasi koruyucu etkisini degerlendirmek amaclanmistir. Gerec ve Yontem: Sprague-Dawley sicanlarda (250-300 gr) soguk-kisitlama stres uygulamasi ile mide ulseri olusturuldu. Stres oncesi 21 gun sureyle SIM (10 mg/kg/day; oral yolla) veya fizyolojik tuzlu su (1 ml; oral yolla) uygulandi. Bir grup sican 21. gunde SIM oncesi selektif olmayan nitrik oksit sentaz (NOS) inhibitoru L-NAME (50 mg/kg; intraperitoneal) veya selektif olmayan siklooksijenaz (COX) inhibitoru indometazin (Indo; 5 mg/kg; subkutan) verildi. Mideler makroskopik ve mikroskopik olarak incelendi ve biyokimyasal analizler icin saklandi. Bulgular: Stres grubunda lezyonlarin siddeti SIM ile azaldi ancak L-NAME veya Indo ile anlamli bir degisiklik gostermedi. Stres mide miyeloperoksidaz aktivitesini kontrol duzeyine kiyasla artirdi (p

The role of losartan and enalapril in the protection against stress-induced gastric mucosal ulceration in rats

Background: Angiotensin II (ANG II) is a stress hormone and its level dramatically increases in the stomach during stress. In addition, it generates reactive oxygen species (ROS) with cellular damage and inflammation. So the aim of this study is to evaluate the mechanism of losartan and enalapril in the prevention of stress-induced gastric ulcer through their action on mucosal prostaglandin (PGs) and antioxidant enzymes and compare between them. Methods: Thirty- six adult male wistar albino rats weighing 180-200 g were divided into 6 groups; n= 6. Groups 1, 2, and 3 were received saline (normal control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks. Groups 4, 5, and 6 were pretreated with saline (ulcer control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks duration. On 29 th day, group 4, 5 and 6 were submitted to gastric ulcer by water immersion method, then animals of all groups were sacrificed, stomachs were excised for gross and microscopic examination and determination of the mucosal levels of prostaglandin E2 (PGE2), superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT). Results: Stress produced gastric ulcer and a significant decrease in all measured gastric parameters compared to normal control group. Pre-treatment of rats with losartan or enalapril decreased the stress-induced alterations in mucosal parameters, but only losartan caused a significant increase in CAT activity in addition. Conclusions: Antagonize the action of ANG II by losartan and enalapril have preventive advantages in stress-induced gastric ulcer and losartan has better influence as it has an additional effect on CAT activity.

Effect of midazolam on gastric secretion and stress-induced gastric ulceration in male albino rats

The term ‘benzodiazepine’ refers to a distinct chemical structure. Benzodiazepines are now used for testing acute anxiety states, and also as a premedication before surgery. Although diazepam is the prototype of benzodiazepine, midazolam is more potent. As peptic ulcers are now being diagnosed more often in school children, and because preanaesthetic management is difficult for children, the use of preoperative sedatives may help to diminish anxiety, minimize psychological trauma and improve the quality of anaesthesia. Midazolam is often used as a preoperative sedative, and during procedures such as endoscopy, where anaesthesia is not required. There is no available data about the effect of various doses of midazolam on gastric secretion and on restraint-induced gastric ulcers in rats. Therefore, the aim of the present study was to study the effect of 0.5, 1 and 2.5 mg/kg of midazolam on gastric secretion and on immobilization-induced gastric stress ulcers in rats. This study was conducted on 48 rats, divided into two big categories, each consisting of 24 rats, which were further divided into four groups, each group consisting of six rats. Administration of midazolam in doses of 0.5 and 1 mg/kg intraperitoneal to pyloric-ligated rats led to a significant decrease in gastric juice volume, acid concentration and the total acid output compared with the control group, which received normal saline. Midazolam administration in a dose of 2.5 mg/kg led to a significant increase in the gastric juice volume, and a significant decrease in the acid concentration and the total acid output compared with the control group. Our results concluded that midazolam administration in a dose of 0.5 mg/kg to children as a prophylactic dose during preanaesthetic medication leads to prevention of aspiration pneumonia, morbidity and mortality of children during endoscopies and elective surgical operations. Restraint-induced stress ulcers approach the ideal technique for ulcer production and testing of antiulcer agents. Our results showed that intraperitoneal administration of midazolam in doses of 0.5, 1 and 2.5 mg/kg to rats in a dose-dependent manner leads to a prophylactic effect against stress-induced gastric ulcers with a protection index of 9.4, 23.8 and 32.2%, respectively. The mechanism of prophylaxis is due to its sedative, anxiolytic and antisecretory effect.

Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats.

Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240mg/kg doses of a standardized 50% methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1β in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.

Gender Based Differences in Stress-induced Gastric Ulcer Formation and its Regulation by Nitric Oxide (NO): An Experimental Study

A variety of physiological and pharmacological factors are known to influence stress responses. Cold restraint stress (CRS) induced gastric ulcerogenesis in both the sexes but such ulceration was found to be markedly higher in male than in female rats. In males, CRS induced significant increases in both ulcer number and ulcer severity; while the females though showed a trend towards increase in both the parameters, the extent of changes was far less than in males. Pre-administration of the NO mimetic, L-Arginine (500 and 1000 mg/kg), prior to CRS, dose dependently decreased ulcer number and severity in male rats. In female rats, L-Arginine also induced a gastric cytoprotective effect during CRS but to a much lesser extent. On the other hand, inhibition of NO synthesis by LNAME (25 and 50 mg/kg) further aggravated such stress ulcerogensis in both males and females, with aggravations being more extensive in males. CRS induced ulcerogenesis was associated with reductions in levels of brain and plasma NOx and GSH levels while MDA levels were elevated in both male and female rats- the magnitude of these changes being higher in males than in females. In female rats, pretreatment with formestane (aromatase inhibitor) but not tamoxifen (estrogen receptor blocker) aggravated stress ulcer formation as compared to vehicle treated CRS exposed rats. Formestane pretreatment also induced greater suppressions in brain NOx and GSH and elevations in brain MDA, as compared to vehicle treated CRS rats. These results indicate that estrogen and its interactions with oxidative stress markers and NO plays a key role in the gender based differences in stress induced gastric ulcerogenesis. It may be speculated that, in males, CRS induces greater reductions in brain NO and enhancement in oxidative injury resulting in greater severity of gastric ulceration. On the other hand, greater resistance of females to ulcerogenic effects of CRS may be due to the protection conferred by estrogen and this effect seems to be related to interactions with brain NO.

Taurine zinc solid dispersions protect against cold-restraint stress-induced gastric ulceration by upregulating HSP70 and exerting an anxiolytic effect

Pharmacological effects of solid dispersions (SDs) of a taurine zinc complex on gastric ulceration and anxiety were investigated. Pretreatment with taurine zinc (50, 100 or 200mg/kg) SDs dose-dependently protected rat gastric mucosa against cold-restraint stress (CRS)-induced gastric injury, and significantly attenuated increases in gastric mucosal H+K+-ATPase activity and lipid peroxidation and enhanced SOD activity. Taurine zinc also inhibited CRS-induced elevation of the serum stress hormones adrenocorticotropic hormone and corticosterone and upregulated HSP70 expression in the gastric mucosa. Moreover, taurine zinc (200mg/kg) SDs more potently protected the gastric mucosa from ulceration than the same dose of taurine, which may be attributed to a synergistic effect between taurine and zinc. Behavioral experiments in mice showed that taurine zinc SDs significantly increased the number of entries and time spent on the open arms in the elevated plus-maze test, time spent in the central area and total distance traveled in the open field test, and time spent and number of entries into the light compartment in the light/dark box test, indicative of reduced anxiety-like behaviors. This study demonstrates taurine zinc protected the gastric mucosa against CRS-induced gastric damage by decreasing oxidative stress, promoting endogenous HSP70 expression and attenuating psychological stress.

Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats

Context: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.Objective: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.Materials and methods: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5 ml/kg once daily ranging from single dose to 30 d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.Results: Boswellia sacra water extract (5 ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p < 0.01) and ulcer score (p < 0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p < 0.01), free acidity (p < 0.01), total acidity (p < 0.01), ulcer index (p < 0.01), and pepsin activity (p < 0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p < 0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2 ml/kg was less proulcerogenic compared with 5 ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.Conclusion: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.

Mastication as a Stress-Coping Behavior.

Exposure to chronic stress induces various physical and mental effects that may ultimately lead to disease. Stress-related disease has become a global health problem. Mastication (chewing) is an effective behavior for coping with stress, likely due to the alterations chewing causes in the activity of the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Mastication under stressful conditions attenuates stress-induced increases in plasma corticosterone and catecholamines, as well as the expression of stress-related substances, such as neurotrophic factors and nitric oxide. Further, chewing reduces stress-induced changes in central nervous system morphology, especially in the hippocampus and hypothalamus. In rodents, chewing or biting on wooden sticks during exposure to various stressors reduces stress-induced gastric ulcer formation and attenuates spatial cognitive dysfunction, anxiety-like behavior, and bone loss. In humans, some studies demonstrate that chewing gum during exposure to stress decreases plasma and salivary cortisol levels and reduces mental stress, although other studies report no such effect. Here, we discuss the neuronal mechanisms that underline the interactions between masticatory function and stress-coping behaviors in animals and humans.

Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

Effect of ulinastatin on Th1/Th2 cell balance in a rat model of stress-induced gastric ulcer

Objective To evaluate the effect of ulinastatin on Th1/Th2 cell balance in a rat model of stress-induced gastric ulcer (GU).Methods Twenty-four male SPF Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number table:control group (group C),stress-induced GU group (group GU) and ulinastatin group (group U).The rats were subjected to water-immersion and restraint stress for 3.5 h to establish GU model in S and U groups.At 10 min before water-immersion,normal saline 0.4 ml and ulinastatin 100 000 U/kg were injected via the tail vein in GU and U groups,respectively.After GU model was established,the abdomen was opened after anesthesia.The whole stomach was exposed,and the gastric mucosal damage was evaluated under microscope,ulcer index (UI) was recorded,and the pathological changes of the gastric mucous membrane were observed.Spleen samples were obtained to detect T-bet,Gata-3,interferon-γ (IFN-γ),and interleukin-4 (IL-4) mRNA expression by RT-PCR.The ratio of T-bet mRNA expression/Gata-3 mRNA expression (T-bet/Gata-3) was calculated.Results Compared with group C,T-bet mRNA expression was significantly down-regulated,Gata-3 mRNA expression was up-regulated,T-bet/Gata-3 ratio was decreased,UI was increased,and no significant changes were found in IFN-γ and IL-4 mRNA expression in GU group,and UI was increased,and no significant changes were found in the other parameters in group U.Compared with group GU,the ratio of T-bet/Gata-3 was significantly increased,and UI was decreased,and no significant changes were found in T-bet,Gata-3,IFN-γ,IL-4 mRNA expression in group U.The gastric mucosal damage was significantly mitigated in GU group as compared with group U.Conclusion The mechanism by which ulinastatin mitigates stress-induced GU may be related to correction of Th1/Th2 cell imbalance in rats. Key words: Trypsin inhibitors; Stomach ulcer; Stress; T-Lymphocytes, helper-inducer

Evaluation of acute toxicity and anti-ulcerogenic study of rhizome starch of two source plants of Tugaksheeree (Curcuma angustifolia Roxb. and Maranta arundinacea Linn.).

Background:Disorders like hyperacidity and gastric ulcers are found very frequently now days because of a faulty lifestyle. Starches (Satwa) obtained from the rhizomes of two plants namely, Curcuma angustifolia Roxb. (Fam. Zingiberaceae) and Maranta arundinacea Linn. (Fam. Marantaceae) are used in folklore practice, as Tugaksheeree, for the treatment of the above-mentioned complaints.Aim:To assess the acute toxicity potential of the C. angustifolia and M. arundinacea along with their assessment for adaptogenic activity, by noting their effect on forced swimming-induced hypothermia and gastric ulceration in rats.Materials and Methods:For acute toxicity study, the effect of test drugs C. angustifolia and M. arundinacea rhizome starch were studied after a single administration of up to three dose levels, with 4400 mg/kg as the maximum dose. The animals were observed for 72 hours periodically and mortality was recorded up to seven days. The adaptogenic and anti-ulcer activities were assessed by determining and comparing the changes in rectal temperature, ponderal changes, ulcer index and histopathological parameters in the test drug group with that of stress control group.Results:Both the drugs did not produce any toxic symptoms or mortality even up to the maximum dose level of 4400 mg/kg. Both the test drugs significantly reversed the stress-induced gastric ulceration in comparison to stress-control rats. Starch from rhizome of C. angustifolia reversed forced swimming-induced hypothermia apparently, but not to a significant extent. However, the reversal of hypothermia found statistically significant in the rhizome starch of the M. arundinacea treated group.Conclusion:M. arundinacea had better anti-stress activity in comparision to C. angustifolia.