Ethanol-induced Gastric Ulcer In Rats Research Articles

Protective Effect of Nigella sativa Seeds Extract against Ethanol-Induced Gastric Ulcer in Rats: Possible Soluble Epoxide Hydrolase Inhibition

Nigella sativa seeds methanolic extract was prepared by a simple maceration process. The extract was subjected to preliminary phytochemical screening and high-performance thin-layer chromatography for linoleic and linolenic acid and tested for in vitro soluble epoxide hydrolase inhibition activity. Then the extract (100, 150 and 200 mg/kg) was evaluated against ethanol-induced stomach ulcer in rats using 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl) urea (1 mg/kg) and omeprazole (20 mg/ kg) as reference standards. The plant extract contains flavonoids, alkaloids, proteins, free amino acids, tannins, flavonoids and linoleic acid. The in vitro soluble epoxide hydrolase inhibition test results reveal that Nigella sativa seeds methanolic extract inhibit human soluble epoxide hydrolase enzyme (half maximal inhibitory concentration=2.619 μg/ml). The Nigella sativa seeds methanolic extract reversed macroscopic and microscopic alteration and attenuated the levels of myeloperoxidase, tumour necrosis factor-alpha, interleukin-6, 5-hydroxyeicosatetraenoic acid in ulcer rats. These results were comparable with standard control. In conclusion, Nigella sativa seeds methanolic extract has a protective action against ethanolinduced ulcers in rats.

Gastroprotective and Antioxidative Effects of the Traditional Thai Polyherbal Formula Phy-Blica-D against Ethanol-Induced Gastric Ulcers in Rats.

Phy-Blica-D is a traditional Thai polyherbal formula that has reduced oxidative stress in non-communicable diseases. However, evidence supporting the gastroprotective effects of Phy-Blica-D has not been previously reported. Therefore, this study aimed to evaluate the gastroprotective effects of Phy-Blica-D against gastric ulcers in rats and investigate the potential underlying mechanism. To estimate the possible mechanisms of action, we examined the levels of oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), as well as antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). According to our results, rats treated with only 80% ethanol (vehicle group) exhibited significant increases in their ulcer area and ulcer index (UI). Moreover, the levels of ROS and MDA markedly increased in the vehicle group compared with the normal control group. Daily oral administration of Phy-Blica-D (500 and 1000 mg/kg) for 7 days not only significantly decreased the ulcer area and UI, but also remarkably decreased the ROS and MDA levels in gastric tissue. Gastric ulcers induced by ethanol had significantly decreased antioxidant enzyme activities (CAT and SOD) and non-enzymatic antioxidant (GSH), whereas pretreatment with Phy-Blica-D significantly improved the activities of CAT, SOD, and GSH. Moreover, after exposure to ethanol, the rats exhibited a significantly increased level of inducible nitric oxide synthase (iNOS), which was reduced after treatment with Phy-Blica-D. These findings suggest that Phy-Blica-D potentially exerts its gastroprotective effects by suppressing oxidative stress and stimulating antioxidant enzymes, which is one of the causes of destruction of cell membranes, and it is involved in the pathogenesis of acute gastric ulcers induced by ethanol.

Therapeutic Potency of Gallium verum Extract on Ethanol-Induced Gastric Ulcer in Rats

Gallium verum, lady's bedstraw is an herbaceous annual plant belonging to the genus Rubiaceae; it possessed antioxidant, cytotoxic for cancer cells, antimicrobial, protective and endocrine effects. This work aimed to investigate the curative effects of G. verum extract on gastric ulcers following absolute ethanol administration in the healthy rat. Eighteen rats were randomly divided into three main groups; rats were fastened for 24 hours before ethanol administration. All groups except control administered ethanol (5 ml/kg body weight; orally). The rats were administrated distilled water (Ulcer group) or G. verum extract (100mg/kg) one hour later. G. verum extract caused a significant decrease in ulcer index, gastric juice volume, malondialdehyde, and nitric oxide, while gastric juice pH, glutathione, glutathione-S-transferase, and catalase increased significantly. The histological lesion score showed a significant enhancement in group G. verum compared to the ulcer group that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB p65 and TNF-α showed a significant decrease in G. verum group. G. verum extract is a promising treatment modality against gastric injury through its powerful antioxidant, acid neutralizing, healing promotion, and ant-inflammation effects.

Evaluation of antioxidant and anti-ulcerogenic effects of Eremurus persicus (Jaub & Spach) Boiss leaf hydroalcoholic extract on ethanol-induced gastric ulcer in rats

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250mg/kg plant extract, and group recipient the dose of 500mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO· and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO·. According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.

Gastroprotective effects of Nelumbinis Rhizomatis Nodus-derived carbon dots on ethanol-induced gastric ulcers in rats.

Aim: To evaluate the gastroprotective effects of Nelumbinis Rhizomatis Nodus carbon dots (NRN-CDs) on ethanol-induced gastric ulcers in rats. Materials & methods: NRN-CDs synthesized and characterized by transmission electron microscopy, ultraviolet, fluorescence and Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, x-ray diffraction and zeta potential analyzer. Their gastroprotective effects toward ethanol-induced gastric ulcers were evaluated in male Sprague-Dawley rats. Results: NRN-CDs showed an average diameter of 2.33±0.42nm and a lattice spacing of 0.29nm. Pretreatment with NRN-CDs significantly decreased the ulcer index and attenuated the severity of gastric mucosal damage, indicating that NRN-CDs exerted potent gastric protective effect. Moreover, the gastroprotection effect was related to the regulation of oxidative stress and inflammatory factors. Conclusion: NRN-CDs could be developed as a potential drug for the treatment of gastric ulcers.

Gastroprotective Effect of Sinapic Acid on Ethanol-Induced Gastric Ulcers in Rats: Involvement of Nrf2/HO-1 and NF-κB Signaling and Antiapoptotic Role.

Background: In the current study, we evaluated the therapeutic potential of sinapic acid (SA) in terms of the mechanism underlying its gastroprotective action against ethanol-induced gastric ulcers in rats. Methods: These effects were examined through gross macroscopic evaluation of the stomach cavity [gastric ulcer index (GUI)], alteration in pH, gastric juice volume, free acidity, total acidity, total gastric wall mucus, and changes in PGE2. In addition, we evaluated lipid peroxidation (malondialdehyde), antioxidant systems (catalase and glutathione), inflammatory markers [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and myeloperoxidase (MPO)], apoptotic markers (caspase-3, Bax, and Bcl-2), nuclear factor-κB [NF-κB (p65)], NO levels, and histopathological staining (H and E and PAS). Results: In rats with ethanol-induced ulcers, pre-treatment with SA (40 mg/kg p. o.) decreased the sternness of ethanol-induced gastric mucosal injuries by decreasing the GUI, gastric juice volume, free acidity, and total acidity. In addition, the pH and total gastric mucosa were increased, together with histopathological alteration, neutrophil incursion, and increases in PGE2 and NO2. These effects were similar to those observed for omeprazole, a standard anti-ulcer drug. SA was shown to suppress gastric inflammation through decreasing TNF-α, IL-6, and MPO, as well as curbing gastric oxidative stress through the inhibition of lipid peroxidation (MDA) and restoration of depleted glutathione and catalase activity. SA inhibited Bcl-2-associated X (Bax) and caspase-3 activity, and restored the antiapoptotic protein Bcl-2; these findings indicate the antiapoptotic potential of SA, leading to enhanced cell survival. SA also repressed NF-κB signaling and increased IκBα. Moreover, SA upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thereby restoring depleted antioxidant defense enzymes and implicating the NRF2/HO-1 signaling pathways. Conclusion: These results suggest that the prophylactic administration of SA (40 mg/kg) can ameliorate ethanol-induced gastric ulcers in rats primarily via the modulation of Nrf2/HO-1 and NF-κB signaling and subsequent enhancement of cell viability.

Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies

Allantoin (ALL) is a phytochemical possessing an impressive array of biological activities. Nonetheless, developing a nanostructured delivery system targeted to augment the gastric antiulcerogenic activity of ALL has not been so far investigated. Consequently, in this survey, ALL-loaded chitosan/sodium tripolyphosphate nanoparticles (ALL-loaded CS/STPP NPs) were prepared by ionotropic gelation technique and thoroughly characterized. A full 24 factorial design was adopted using four independently controlled parameters (ICPs). Comprehensive characterization, in vitro evaluations as well as antiulcerogenic activity study against ethanol-induced gastric ulcer in rats of the optimized NPs formula were conducted. The optimized NPs formula, (CS (1.5% w/v), STPP (0.3% w/v), CS:STPP volume ratio (5:1), ALL amount (13 mg)), was the most convenient one with drug content of 6.26 mg, drug entrapment efficiency % of 48.12%, particle size of 508.3 nm, polydispersity index 0.29 and ζ-potential of + 35.70 mV. It displayed a sustained in vitro release profile and mucoadhesive strength of 45.55%. ALL-loaded CS/STPP NPs (F-9) provoked remarkable antiulcerogenic activity against ethanol-induced gastric ulceration in rats, which was accentuated by histopathological, immunohistochemical (IHC) and biochemical studies. In conclusion, the prepared ALL-loaded CS/STPP NPs could be presented to the phytomedicine field as an auspicious oral delivery system for gastric ulceration management.

Allanblackia floribunda Seed Extract Attenuates the Ethanol-Induced Gastric Ulcer in Rats via the Inhibition of TNF-α and INF-γ Levels and Modulation in the Expression of Ki67 Protein.

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p < 0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.

Gastroprotective effect of mucilage fraction from Solenostemma argel via cytoprotection and attenuation of oxidative stress, inflammation and apoptosis

Introduction: Polysaccharides have numerous therapeutic values including immunity stimulation, angiotensin converting enzyme inhibition, wound healing, anti-diabetic and cytotoxic activities, in addition to their potent anti-oxidant properties. This work examined the gastroprotective and ulcer healing potential of mucilage fraction isolated from Solenostemma argel (Delile) Hayne (MFA) against ethanol-induced gastric ulcer in rats. Methods: Forty Sprague-Dawley rats were divided into five groups (n=8); normal control (I), ethanol control (II), 20 mg/kg Antodine pretreated rats (III), 100 mg/kg, and 200 mg/kg MFA pretreated rats, respectively (IV &amp; V). All rats in groups II-V received single intragastric dose of ethanol (5 mL/kg) to induce gastric ulcer. Gastric mucosal injuries were assessed by stomach gross examination as well as histopathology, and immunohistochemistry of apoptotic markers. Also, several biochemical parameters including oxidative stress, proinflammatory cytokines, cytoprotective and cell proliferative biomarkers were measured. Results: High-performance liquid chromatography (HPLC) analysis of MFA revealed its composition of glucose, D-fucose and N-acetyl glucosamine as monosaccharaides, in addition to glucuronic and galacturonic acids. The data showed that MFA, 200 mg/kg had potent antioxidant, anti-inflammatory, cytoprotective, cell proliferative, and antiapoptotic activities which were better than Antodine. Conclusion: This study revealed that MFA had significant gastroprotective effects against ethanol-induced gastric injuries and could be a promising adjuvant therapy for ulcer treatment.

Protective effects of polysaccharides from Panax ginseng on acute gastric ulcers induced by ethanol in rats.

Panax ginseng is a traditional medicine used in China to treat many diseases. Polysaccharides are primary active components and have many pharmacological effects. Gastric ulcer is a serious gastrointestinal disease. However, whether polysaccharides influence gastric ulcers is unclear. In this study, the effective gastroprotective impacts and potential mechanisms of Panax ginseng polysaccharides (GPS) on gastric damage induced by ethanol in rats were investigated by macroscopically evaluating gastric mucosal injuries (improved ulcer index (UI)), histopathological staining (H&E and PAS), increased NO and PGE2 levels, and suppression of oxidative stress (increased superoxide dismutase (SOD) and catalase (CAT) and decreased malondialdehyde (MDA)) and inflammation (reduced tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and myeloperoxidase (MPO)). Pretreatment with GPS ameliorated the expression of I-κB/NF-κB and JAK/STAT proteins in the rat stomach exposed to ethanol. The results indicated that GPS prevent ethanol-induced gastric injuries in rats by predominantly suppressing gastric inflammation and oxidative stress through NF-κB and STAT inhibition.

Persimmon (Diospyros Kaki L.) Alleviates Ethanol-Induced Gastric Ulcer in Rats

Persimmon (Diospyros Kaki L.) Alleviates Ethanol-Induced Gastric Ulcer in Rats

In vitro antioxidant activity and gastroprotective effect of ethanolic extract from Cucumis melo L. var. inodorus fruit on ethanol-induced gastric ulcer in rats

The aim of this study was to estimate the content of polyphenols, flavonoids and tannins and to evaluate the antioxidant property and the antiulcer activity of the ethanolic extract of melon (Cucumis melo L. var. inodorus) pulp on ethanol-induced gastric ulcers in rats. Ferric reducing power and hydroxyl radical scavenging tests were applied to evaluate the in vitro antioxidant activity. The polyphenolic and flavonoids contents of melon extract were found to be 56.5 ± 2.49 mg GAE/g of dry extract and 0.43 ± 0.09 mg QE/ g of dry extract, respectively. Whereas the tannins content was 48. 30 ± 0. 9 mg ETA/ g of dry extract. Melon pulp extract exhibited a good reducing potential with an EC50 of 4.23 ± 0.08 mg/ml and high hydroxyl radical scavenging activity with IC50 of 1.83± 0.09 mg/ml. Oral administration of the melon pulp extract at doses of 200 and 600 mg/kg to rats reduced gastric mucosal lesions dose-dependently with percentage protection of 56.56 and 93.79% compared to omeprazole (95.92 %) as reference drug. These results showed that the melon pulp extract had a good antioxidant activity and gastroprotective potential suggesting it use as an adjuvant in the treatment of gastric ulcer.&#x0D; Keywords: Cucumis melo var. inodorus, Polyphenols, Flavonoids, Tannins, Ulcer, Rat.

Gastroprotective effect of Lycium barbarum polysaccharides and C-phycocyanin in rats with ethanol-induced gastric ulcer

This study investigated the gastroprotective effect of Lycium barbarum polysaccharides (LBP) and C-phycocyanin (C-PC) in rats with ethanol-induced gastric ulcer. Rats were divided into 5 groups: normal, ulcer, ulcer treated with 100 mg/kg bw LBP, ulcer treated with 50 mg/kg bw C-PC, and ulcer treated with 50 mg/kg bw LBP and 25 mg/kg bw C-PC. Pretreatment with LBP and/or C-PC was given a week before ulcer induction. Ulcer induction was produced by 50% ethanol administration orally every other day for 4 weeks. After 5-week treatment, the histopathological observation showed that LBP or C-PC attenuated the severity of gastric mucosal damage. LBP decreased serum malondialdehyde (MDA) levels and gastric interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) levels, and myeloperoxidase (MPO) activity. C-PC decreased serum MDA levels and gastric tumor necrosis factor-α (TNF-α), IL-1β, IL-6, ICAM-1 levels, and MPO activity. Combined LBP and C-PC decreased serum MDA levels and gastric TNF-α, IL-1β, IL-6, and ICAM-1 levels. LBP and/or C-PC increased gastric heat shock protein 70 and non-protein sulfhydryl compounds. Rats with ulcer and treatment had enriched with the family Bacillaceae. Therefore, pretreatment with LBP and/or C-PC attenuated ethanol-induced gastric ulcer in rats via suppressing oxidation and inflammation and increasing gastroprotection.

Natural deep eutectic solvent (NADES)-based blueberry extracts protect against ethanol-induced gastric ulcer in rats

Blueberry is a polyphenol-rich fruit bearing great bioactive potential. Natural deep eutectic solvents (NADES) emerged as putatively biocompatible solvents that could substitute for toxic organic solvents in the extraction of fruit phenolic compounds for developing nutraceuticals or functional foods. Therefore, the aim of this study was to investigate the gastroprotective effects and the biocompatibility of a blueberry crude extract (CE) obtained using NADES and of the extract fractions (anthocyanin-rich fraction – ARF; non-anthocyanin phenolic fraction - NAPF) in a model of ethanol-induced gastric ulcer in rats. CE was the NADES-containing, ready-to-use extract that was obtained using choline chloride:glycerol:citric acid NADES (0.5:2:0.5 M ratio). ARF and NAPF were the NADES-free fractions obtained by solid phase purification of CE and were investigated to identify the bioactive fraction responsible for the effects of CE. Animals were treated for 14 days with water, NADES vehicle, CE, ARF, NAPF or lansoprazole (intragastric) and then received ethanol to induce gastric ulcer. CE decreased ulcer index and preserved the integrity of gastric mucosa. The pretreatment with CE or ARF reduced glutathione depletion and the inflammatory response. All treatments, including NADES vehicle reduced protein oxidation and nitric oxide overproduction in ethanol-treated rats. Additionally, ARF increased short-chain fatty acids in feces. These findings suggest that NADES can be used to obtain biocompatible extracts of blueberry that exhibit gastroprotective effects with no need of solvent removal. The gastroprotective effects were mainly associated to ARF but NAPF and even NADES vehicle also contributed to some protective effects.

A potential drug combination of omeprazole and patchouli alcohol significantly normalizes oxidative stress and inflammatory responses against gastric ulcer in ethanol-induced rat model

Omeprazole (OME) is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, OME may cause some inevitable side effects and the long-term consequences of OME could increase the risk of diarrhea. Patchouli Alcohol (PA), the main extract of Pogostemonis Herba, have demonstrated benefits in treating gastric ulcer (GU) with low toxicity. The present study aimed to investigate the synergistically protective effects of OME and PA against ethanol-induced GU in rats to study the involvement of antioxidant and anti-inflammatory activities. Moreover, the anti-apoptosis, anti-oxidant and anti-inflammatory effects in H2O2-induced gastric epithelial cells (GES-1) and LPS-induced RAW264.7 cells were determined, as well as the modulation of signaling proteins. The results demonstrated that PA alone or combined with OME provided remarkable benefits by reducing ulcer areas, modulating oxidant stress and inflammatory factors and the therapeutic efficacy was showed to be dose-dependent, which were partly superior to that of high-dose OME only. Additionally, co-treated regimen could superiorly down-regulate cell apoptosis and regulate the levels of oxidant activities and inflammatory cytokines on H2O2-induced GES-1 cells and LPS-induced RAW264.7 cells, which involved with cleaved caspase 3, Bcl-2 and BAX protein expressions and MAPK pathway. We provided a new understanding that the combination of OME and PA possessed gastroprotective effects on modulating cell apoptosis, antioxidant stress and anti-inflammatory responses against GU. Therefore, PA was inferred to take a potential and critic role in gastric mucosa protection.

Synthesis, gastroprotective and acute toxicity of bio-isosteric derivative of diclofenac

Background and objective: Non-steroidal anti-inflammatory drugs (such as diclofenac1) had been widely prescribed for the treatment of different types of pain; however, they are not devoid of adverse effects. Therefore, synthesis of new bio-isosteric analogs4a-e of diclofenac1 with greater COX II selectivity and less gastrointestinal side effect is demanded. This study aimed to evaluate the acute toxicity and gastroprotective activity of the bio-isosteric derivative of diclofenac against ethanol-induced gastric ulceration in rats. Methods: 2-Cumaranone 2 had been utilized to prepare amides 3a-e then after the bio-isosteric derivatives 4a-esynthesized from them then used to study the biological activity by testing whether high doses of the prototype compound 4c are toxic or not on albino mice and measuring the gastroprotective effect on albino rats. Rats were divided into four groups. Group 1 orally administered with Tween 20; group 2 was orally administered with 20 mg/kg esomeprazole; groups 3 and 4 received 100 and 200 mg/kg of the compound, respectively. Absolute ethanol was given orally to the groups, and rats were sacrificed after one hour. Results: Few diarylethers 4a-ebio-isosteric to diclofenac had been prepared and fully characterized (including 1HNMR, 13CNMR, and IR spectroscopy). Serum biochemical parameters were reported to be normal. Hematological analysis of kidney and liver did not elicit any remarkable changes in the treated group compared to the control group. Thus, the 50% oral lethal dose (LD50) for the male and female mice was greater than 5 g/kg body weight. Anti-ulcer data showed a gastroprotective effect of the bio-isosteric diclofenac derivative 4c and presented the ulcer area inhibition, low stomach pH, and preserve the mucous content. Conclusion: Many bio-isosteric derivatives of diclofenac had been prepared with good yields. The synthesized derivative4c showed no toxicity, and the gastroprotective effect may possibly be due to the preservation of gastric wall mucus.

Metabolomic profiling of five Agave leaf taxa via UHPLC/PDA/ESI-MS inrelation to their anti-inflammatory, immunomodulatory and ulceroprotective activities

Agave plants are popular for their myriad applications in traditional medicine attributed to their reported anti-inflammatory, immunomodulatory, cytotoxic and antifungal activities. The aim of this study was to examine the anti-inflammatory, immunomodulatory and ulceroprotective activity of Agave species in relation to their metabolite fingerprint via a metabolome based ultra-performance liquid chromatography-mass spectrometry (UPLC–MS) approach coupled to chemometrics. The metabolomic differences among five examined Agave leaves viz. Agave americana L., A. americana var. marginata Trel, A. angustifolia Haw. cv. marginata, A. desmettiana Jacobi, A. pygmaea Gentry were determined via a total of 56 annotated metabolites. Identification based on MSn and UV spectra revealed 25 steroidal saponins and sapogenins, 6 flavonoids, 2 homoisoflavonoids, 7 phenolic acids, 6 fatty acids and 3 fatty acid amides, some of which are reported for the first time in Agave. Metabolites heterogeneity was assessed among leaf taxa via multivariate data analyses for samples classification, showing that saponins is the major metabolite contributing to their classification. The carrageenan induced acute inflammatory rat model was used to assess the anti-inflammatory activity of Agave extracts via monitoring of blood cytokine levels. Additionally, their effects on ethanol-induced gastric ulcer in rats were evaluated. A. pygmaea showed the most significant anti-inflammatory and immunomodulatory activity, while A. angustifolia var. marginata possessed the highest ulceroprotective activity, which could be attributable to the high abundance of various saponins and homoisoflavonoids in those taxa.

Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.

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

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

Fisetin attenuates gastric mucosal lesions through modulating nuclear factor-kappa B and peroxisome proliferator-activated receptor-γ in rats

Background: Nowadays, the use of plant extracts is increasing in the world for the prevention and treatment of ulcer. Objective: The objective of this study was to explore the underlying mechanism of action of fisetin on ethanol-induced gastric ulcer model. Materials and Methods: In this study, gastric mucosal lesions were induced by ethanol in rats. Five groups of rats were formed based on the treatment administered: model group (model), omeprazole (40 mg/kg) group (omeprazole), high-dose fisetin group (100 mg/kg, H-fisetin), medium-dose fisetin group (50 mg/kg, M-fisetin), and low-dose fisetin group (25 mg/kg, L-fisetin). Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels were assessed in serum. The expression of peroxisome proliferator-activated receptor (PPAR)-γ, nuclear factor-kappa B (NF-κB), and p38-mitogen-activated protein kinase (p38-MAPK) in the gastric mucosa was also measured. Results: In the case of the high-dose fisetin group, the level of TNF-α, IL-1β, and IL-6 decreased from 9.57 pg/mL to 5.19 pg/mL, from 0.59 pg/mL to 0.27 pg/mL, and from 37.96 pg/mL to 21.09 pg/mL, respectively. In the case of the omeprazole group, the level of TNF-α, IL-1β, and IL-6 decreased to 4.38 pg/mL, 0.27 pg/mL, and 18.58 pg/mL, respectively. The expression of PPAR-γ protein in the high-dose fisetin and omeprazole groups was about 1.5 times higher than that in the model group. Compared with the model group, the expression of NF-κB protein reduced to 0.34 level and 0.47 level in the omeprazole and high-dose fisetin groups, respectively. Compared with the model group, the expression of p38-MAPK protein reduced to 0.55 level and 0.68 level in the omeprazole and high-dose fisetin groups, respectively. Conclusion: Fisetin might relieve the symptoms of ethanol-induced gastric ulcer in rats through the regulation of NF-κB pathway.