Anti-ulcer and antioxidant activity of GutGard

The present study was undertaken to determine the anti-ulcer and antioxidant potential of GutGard, a standardized extract of Glycyrrhiza glabra commonly known as licorice. Effect of various doses (12.5, 25, and 50 mg/kg, po) of GutGard was studied on gastric ulcers in pylorus ligation-, cold-restraint stress- and indomethacin induced gastric mucosal injury in rats. Anti-ulcer activity was evaluated by measuring the ulcer index, gastric content, total acidity, and pH of gastric fluid. GutGard dose dependently decreased gastric content, total acidity, ulcer index and increased pH of gastric fluid in pylorus ligation ulcer model. In cold-restraint stress- and indomethacin induced ulcer models all the doses of GutGard decreased the ulcer index and increased the pH of gastric fluid. The antioxidant activity was evaluated by the oxygen radical absorbance capacity (ORAC) assay. GutGardT exhibited potent antioxidant activity with high hydrophilic and lipophilic ORAC value. GutGard possessed anti-ulcerogenic properties that might be afforded via cytoprotective mechanism by virtue of its antioxidant properties. These results supported the ethnomedical uses of licorice in the treatment of gastric ulcer.     

Role of nuclear factor-kappaB in gastric ulcer healing in rats

We investigated the role of nuclear factor-kappaB (NF-kappaB) in gastric ulcer healing in rats. NF-kappaB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-kappaB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1beta activated NF-kappaB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-kappaB action resulted in suppression of both their mRNA expression and increases in PGE(2) and CINC-1 levels induced by interleukin-1beta. Persistent prevention of NF-kappaB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1beta, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE(2) production were also reduced. These results demonstrate that NF-kappaB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.     

大鼠脑内5-羟色胺在应激性溃疡形成中的作用

通过神经化学和神经药理学的方法,在大鼠观察了冷冻加束缚应激性溃疡的形成过程中,脑内5-羟色胺(5-HT)的作用。结果如下:1.在应激过程中,脑内5-HT 及其主要代谢产物5-羟吲哚乙酸(5-HIAA)的含量明显升高,特别是5-HIAA 的含量随着应激时间的延长持续上升,说明5-HT 的代谢加快。2.脑内5-HT 或5-HIAA 含量在应激45min 时与溃疡指数呈明显的负相关,而在应激180min 时则与溃疡指数呈明显的正相关。3.侧脑室注射5-HT或其前体5-羟色氨酸(5-HTP),对应激性溃疡的形成呈双重作用,小剂量时减轻而大剂量时加重溃疡的形成。4.腹腔注射5-HT 合成阻断剂对氯苯丙氨酸(pCPA)可降低大鼠脑内5-HT 和5-HIAA 含量,使应激60min 鼠的溃疡形成加重,而使应激180min 鼠的溃疡形成减轻。以上结果提示,在大鼠的冷冻加束缚应激性溃疡的形成过程中,脑内5-HT 起着一定的作用,它很可能在应激早期减轻而在应激晚期加重溃疡的形成。     

Gastroprotective effect of Terminalia arjuna bark on diclofenac sodium induced gastric ulcer

AIM: The present study was aimed to evaluate the effect of methanolic extract of Terminalia arjuna (TA) on diclofenac sodium induced gastric ulcer in experimental rats. METHODS: Animals were induced for gastric ulcer with diclofenac sodium (DIC) (80mg/kg bodyweight in water, orally) and treated orally with TA in various doses ranging from 100mg/kg bodyweight to 500mg/kg bodyweight. The effective dose was 400mg/kg bodyweight, since this dose elicited a maximum reduction in lesion index. The gastroprotective effect of TA was assessed from volume of gastric juice, pH, free and total acidity, pepsin concentration, acid output in gastric juice, the levels of non-protein sulfhydryls (NP-SH), lipid peroxide (LPO), reduced glutathione (GSH), and activities of enzymic antioxidants--super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and myeloperoxidase (MPO) in gastric mucosa. The levels of DNA, protein bound carbohydrate complexes--hexose, hexoseamine, sialic acid, fucose in gastric mucosa and gastric juice and the levels of RNA in gastric mucosa were assessed. The stomach tissues were used for adherent mucus content and also for the histological examination. RESULTS: A significant reduction in lesion index was observed in ulcer induced animals treated with TA (DIC+TA) compared to ulcerated rats (DIC). A significant increase was observed in pH, NP-SH, GSH, enzymic antioxidants, protein bound carbohydrate complexes, adherent mucus content, nucleic acids with a significant decrease in volume of gastric juice, free and total acidity, pepsin concentration, acid output, LPO levels and MPO activities in DIC+TA rats compared to DIC rats. Histological studies confirmed the gastroprotective activity of TA. CONCLUSION: From the data presented in this study it could be concluded that T. arjuna acts as an gastroprotective agent probably due to its free radical scavenging activity and cytoprotective nature.     

Central inhibitory effect of Moringa oleifera root extract: possible role of neurotransmitters

Effect of chronic treatment of standardized aqueous extract of Moringa oleifera (MO) root (100, 200, 300, 350, 400, 450 mg/kg; po) on penicillin (PCN) induced convulsion, locomotor behaviour, brain serotonin (5-HTT), dopamine (DA) and norepinephrine (NE) level was studied in Holtzman strain adult albino rats. The result revealed that pretreatment with MO inhibited PCN-induced seizure and markedly reduced locomotor activity. Chronic treatment with MO significantly increased the 5-HT and decreased the DA level in cerebral cortex (CC), midbrain (MB), caudate nucleus (CN) and cerebellum (CB). NE level was significantly decreased in CC but no appreciable change was observed in MB, CB and CN. Thus the central inhibitory effect of MO is discussed in the light of the disturbed balance between 5-HT, DA and NE.     

Role of 5-hydroxytryptamine in Moringa oleifera induced potentiation of pentobarbitone hypnosis in albino rats

The role of 5-hydroxytryptamine (5-HT) in pentobarbitone (PB) sleeping time, gross behaviour, electrical activity of the brain and serum 5-HT level was studied in Holtzman strain adult albino rats following treatment with M. oleifera (MO). MO (350mg/kg) caused inhibition of awareness, touch response, motor activity, righting reflex, and grip strength. It significantly increased the PB sleeping time, serum 5-HT level (P<0.001) and alpha-wave activity. These observations indicate that the aqueous extract of MO potentiated PB induced sleeping time and increased the alpha-wave activity through 5-HT.     

Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration.     

Reduction of asymmetric dimethylarginine in the protective effects of rutaecarpine on gastric mucosal injury

Our recent study has shown that asymmetric dimethylarginine (ADMA) plays an important role in facilitating gastric mucosal injury by multiple factors. To explore whether the protection of rutaecarpine against gastric mucosal injury is related to reduction of ADMA content, a model of ethanol-induced gastric mucosal injury in rats was selected for this study. The ulcer index, the content of ADMA and NO, and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in gastric tissues were measured in vivo after pretreatment with rutaecarpine. The in vitro effect of rutaecarpine on the release of calcitonin gene-related peptide (CGRP) and NO from isolated gastric tissues was also determined. The results showed that ethanol significantly increased the ulcer index, decreased the DDAH activity and the NO level, and elevated the ADMA level, which was attenuated by pretreatment with rutaecarpine (0.6 mg/kg or 1.2 mg/kg). In the isolated gastric tissues, rutaecarpine significantly increased the release of both CGRP and NO; the release of NO, but not CGRP, was abolished in the presence of l-NAME (10(-4) mol/L). The present results suggest that rutaecarpine protects the gastric mucosa against injury induced by ethanol and that the gastroprotection of rutaecarpine is related to reduction of ADMA levels through stimulating the release of CGRP.     

Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats

Centella asiatica is commonly mentioned as a Rasayana in Ayurveda, an ancient system of Indian medicine for various ailments including abdominal disorders. Rasayanas have been advocated for use in rejuvenation therapy. The present study was conducted to evaluate the possible anti-ulcerogenic activity of fresh juice of C. asiatica (CAJ) against ethanol-, aspirin-, cold-restraint stress- and pyloric ligation induced gastric ulcers in rats. The drug given orally in doses of 200 and 600 mg/kg twice daily for five days, showed significant protection against all the above experimental ulcer models and the results were comparable with those elicited by sucralfate (SF, 250 mg/kg, p.o., BD x 5 days). CAJ showed little or no effect on offensive acid-pepsin secretion. However, at 600 mg/kg CAJ significantly increased gastric juice mucin secretion and increased the mucosal cell glycoproteins signifying increase in cellular mucus. It also decreased cell shedding indicating fortification of mucosal barrier. Thus, the ulcer protective effect of CAJ may be due to strengthening of the mucosal defensive factors.     

Effect of standardized extract of Ocimum sanctum Linn. on gastric mucosal offensive and defensive factors

The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.     

Regional distribution of dopamine, 5-hydroxytryptamine,and noradrenaline in the rat vas deferens

The concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in the rat vas deferens divided in eight or four sections were determined by high performance liquid chromatography with electrochemical detection. Dopamine and NA had the same regional distribution; their concentrations were maximal near the prostatic end and decreased towards the epididymis. The concentration of 5-HT also decreased from the prostatic to the epididimal end, but 5-HT did not follow the same regional distribution as DA and NA. Reserpine (0.02 or 0.2 mg/kg, i.p., 24 hr) and 6-hydroxydopamine (2×80 mg/kg, i.v., 6 days) decreased the contents of DA and NA; the concentrations of both amines were modified to a similar extent. Reserpine also diminished the content of 5-HT. Pargyline (200 mg/kg, i.p., 2 hr) increased the concentration of 5-HT whilep-chlorophenylalanine (300 mg/kg, oral, 3 days) decreased the contents of the amine in some sections of the vas deferens. This study suggests that DA and NA co-exist in the same sympathetic neurons. Some of the 5-HT could be stored in mast cells as previously proposed, but the finding that tissue content of 5-HT changes after inhibiting the deamination or synthesis of the amine suggests that other source(s) of 5-HT distinct from mast cells exist in the rat vas deferens.     

Involvement of heat shock proteins in the healing of acetic acid-induced gastric ulcers in rats.

The present study examined the expression of 73-kDa of heat shock cognate protein (HSC70), 72-kDa of heat shock protein (HSP70) and 47-kDa of HSP (HSP47) observed in the ulcer healing process in rats. Gastric ulcers were induced by a luminal application of acetic acid in male Donryu rats. During the ulcer healing process, the expression of HSPs in the ulcerated tissue was determined. A high level of HSC70 expression was observed both in the normal mucosa and ulcerated tissue, but the level did not change upon ulceration and ulcer healing. While HSP70 and HSP47 were markedly expressed in the ulcer base during ulceration, and decreased with ulcer healing. HSP70 expression in the ulcer margin was gradually increased with ulcer healing. Omeprazole accelerated the healing of gastric ulcers with strong inhibition of gastric acid secretion, while indomethactin delayed in ulcer healing despite slight inhibition of gastric acid secretion. Omperazole enhanced the expression of HSP70 both in the ulcer margin and base, but it reduced HSP47 expression in the ulcer base Indomethacin markedly enhanced HSP47 expression only in the ulcer base. In conclusion, the expression of HSP70 and HSP47 is changed during ulcer healing. Furthermore, it was suggested that the enhanced expression of HSP70 is involved in acceleration of ulcer healing, but overexpression of HSP47 is involved in delayed ulcer healing.     

Gastroprotective effect of leptin in indomethacin-induced gastric injury

This study investigated the involvement of neutrophil infiltration, disturbances in nitric oxide (NO) generation and oxidative stress in indomethacin-induced gastric ulcer, and the possible gastroprotective potentials of leptin, known for its angiogenic effect. Male Wistar albino rats (180–220 g) were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg/kg p.o.) and an ulcer group pretreated with leptin (10 μg/kg i.p. 30 min before ulcer induction). The animals were killed 6 h after indomethacin administration and their gastric juice, serum and mucosal tissue were used for gastric injury evaluation. Indomethacin produced multiple lesions in glandular mucosa, evidenced by marked increase in gastric ulcer index (GUI) accompanied by significant increases in gastric juice acidity, tissue myeloperoxidase (MPO) activity, serum NO and tissue conjugated diene (CD), and marked decreases in tissue NO and glutathione (GSH) as well as glutathione reductase (GR) and superoxide dismutase (SOD) activities, while gastric juice mucin and tissue glutathione peroxidase (GPx) were not affected. Leptin exerted significant gastroprotection as evidenced by significantly decreased GUI and attenuated neutrophil infiltration. Leptin significantly increased mucin and tissue NO, restored GR and SOD activities and up-regulated GPx activity. It failed to affect acidity, serum NO, GSH and CD. These results suggest that leptin confers significant gastroprotection against indomethacin-induced injury through interfering with neutrophil infiltration, NO production and oxidative stress.     

Role of capsaicin sensory nerves and EGF in the healing of gastric ulcer in rats

Accumulating evidence indicates that capsaicin sensitive afferent fibers play a pivotal role not only in gastroprotection but also in ulcer healing. Denervation of capsaicin sensitive afferent fibers exerts an adverse action on these effects. However, whether such an action is mediated through a depression on epidermal growth factor (EGF) is undefined. In this study, the effects of denervation of sensory neurons with capsaicin (100 mg/kg, s.c.) on acetic acid-induced chronic gastric ulcers and their relationship with the EGF expression in salivary glands, serum and gastric mucosa were investigated. Capsaicin significantly increased ulcer size, decreased gastric mucosal cell proliferation at the ulcer margin, angiogenesis in the granulation tissue and also gastric mucus content. Ulcer induction by itself dramatically elevated EGF levels in salivary glands and serum on day 1 and 4, and also in the gastric mucosa on day 4. However, capsaicin completely abolished these effects. It is concluded that stimulation of EGF expression in salivary glands and serum may be one of the mechanisms by which capsaicin sensitive nerves contribute to the gastroprotective and ulcer healing actions in the stomach.     

Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior.

Corticosterone, 1.0 and 5.0 mg/kg, improved passive avoidance behavior based on fear versus thirst-conflict situation. Corticosterone, 1.0 mg/kg, increased the serotonin (5-HT) content in the hypothalamus and mesencephalon; 5.0 mg/kg of corticosterone had no effect. Plasma corticosterone level increased in a dosedependent manner after corticosterone treatment. dl-Parachlorophenylalanine (PCPA) impaired passive avoidance behavior and decreased the hypothalamic and mesencephalic 5-HT level. After PCPA treatment, the plasma corticosterone level was slightly increased. PCPA pretreatment was able to prevent the action of 1.0 and 5.0 mg/kg of corticosterone on behavior as well as on brain 5-HT level. Corticosterone, 10.0 mg/kg, impaired passive avoidance behavior, decreased the hypothalamic and mesencephalic 5-HT content, and increased the plasma corticosterone level.Monoamine oxidase inhibitor (nialamide) treatment improved the passive avoidance behavior and increased the 5-HT level in the hypothalamus and mesencephalon. The plasma corticosterone level did not change significantly. Nialamide pretreatment abolished the behavioral action of 10.0 mg/kg of corticosterone as well as its action on brain 5-HT level. A large dose of corticosterone (25.0 mg/kg) and 2.5 mg/kg of 6-dehydro-16-methylenhydrocortisone (6DH) had a similar action on passive avoidance behavior and on brain serotonin level as 10.0 mg/kg of corticosterone; however, the plasma corticosterone level was increased only in corticosterone-treated animals and was significantly decreased after 6DH. 11-Deoxycorticosterone (DOC) at a dose of 25.0 mg/kg was ineffective on passive avoidance behavior and on brain serotonin content, whereas it slightly decreased the plasma corticosterone level. Data suggest that the corticosterone has dosedependent dual action on passive avoidance behavior, and its action is, at least partly, mediated via changed brain serotonin metabolism. The action seems to be a glucocorticoid-specific one since mineralocorticoid (DOC) is ineffective on this behavioral pattern.     

Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats

Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague?CDawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1?ml/rat), oleuropein group (12?mg/kg), and oleuropein (6, 12, and 18?mg/kg) plus ethanol groups, as well as ranitidine (50?mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18?mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6?mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12?mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18?mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages.     

Gastro-protective effect of methanol extract of Ficus asperifolia bark on indomethacin-induced gastric ulcer in rats

The gastro-protective and antioxidant effects of methanol extract of Ficus asperifolia bark on indomethacin induced gastric ulcer were investigated in male rats. Thirty two male rats divided into 4 equal groups and were treated as follows: group1 (control), 0.5ml of 5% tween 80 (vehicle for the extract), groups 2 and 3, 100 and 500mg/kg of Ficus asperifolia extract respectively and group 4, cimetidine (100mg/kg). After two weeks of daily oral administration of vehicle, extract or cimetidine, gastric ulcer was induced in all rats with indomethacin (40 mg/kg, p.o). Gastric juice pH, gastric acid concentration, gastric ulcer score, percentage gastric ulcer inhibition, activity levels of superoxide dismutase (SOD), catalase and malondiadehyde (MDA) were determined. Ficus asperifolia extract significantly increased gastric pH (p.     

Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats

Background: Medications to prevent the development of NSAID-induced gastric ulcers have a large range of unpleasant side effects. Recent efforts have been focused on determining safer alternative nontoxic and natural forms of anti-ulcer treatments. Methods:Twenty-four male rats were divided into 4 groups: 1: control group that received no treatment; 2: the ndomethacin-treated group that received 20 mg/kg of indomethacin for 2 days to induce the development of gastric ulcers; 3: quercetin-treated group that in addition to the indomethacin treatment, received 50 mg/kg of quercetin 6 hours after and then daily for 14 days and; 4: the melatonin-treated group which received 20 mg/kg of melatonin 6 hours after each indomethacin treatment and then daily for 14 days. All drugs were administered orally. The following parameters were assessed in each group: mean ulcer index of gastric tissue, gastric acid volume and pH, oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH), inflammatory markers: PGE-2, TNF-α, and IL-10, nitric oxide (NO) levels and the relative gene expression of BAX, BCL-2 and COX-2 by real time PCR.Results:Our findings revealed that the indomethacin-treated group had a significantly increased (p< 0.05) ulcer index, gastric acid volume, and elevated levels of stress, inflammatory, and apoptotic markers compared to controls. In the groups that received quercetin or melatonin, these factors were all significantly decreased (p< 0.05). Between quercetin and melatonin, there was no significant difference in their gastroprotective effect. Conclusion:Both quercetin and melatonin had protective antioxidant, anti-inflammatory and antiapoptotic activity against indomethacin-induced gastric ulcers.Key Words: Gastric ulcer, Indomethacin, Melatonin, Quercetin     

Gastroprotective effects of Polygonatum odoratum in rodents by regulation of apoptotic proteins and inflammatory cytokines

In an increasing interest in natural antiulcer compounds that may have gastric healing effects and possibly prevent ulcer recurrence, Polygonatum odoratum appears as a strong candidate. The gastroprotective potentials of P. odoratum rhizome extract (PORE) were explored on ethanol-induced gastric ulceration in rats. Sprague Dawley rats were caged in 5 groups, normal and ulcer control rats received CMC (1% carboxymethyl cellulose). Omeprazole (20 mg/kg) was given to reference Rats. Experimental rats were treated with 250 mg/kg and 500 mg/kg PORE, respectively. After an hour, the normal control rats received 1% CMC, whereas rat groups 2–5 were given absolute ethanol by oral gavage. After 60 min, rats received anesthesia and were sacrificed. Dissected gastric tissue was analyzed by histopathological and immunohistochemical techniques. PORE treatment significantly lowered the ethanol-induced gastric injury, as shown by up-surging gastric pH and mucus content, reduced leukocyte infiltration, lower ulcerative areas in mucosal layers, and increased antioxidants (SOD and CAT) and (MDA) levels. Furthermore, PORE pre-treated rats showed significantly increased expression of the Periodic acid-Schiff (PAS), HSP-70 protein, and decreased Bax protein in their gastric epithelial layers. PORE treatment showed an important regulation of inflammatory cytokines shown by decreasing the TNF-a, and IL-6 and increasing the IL-10 values. The detected biological activity of PORE is encouraging and presents the scientific evidence for its traditional use as a gastroprotection agent however further studies are required to determine the exact phytochemicals and mechanism pathway responsible for this bioactivity.