Comprehensive fecal metabolomics and gut microbiota study of the protective mechanism of herbal pair Polygonum hydropiper-Coptis chinensis in rats with stress-induced gastric mucosal damage.

Introduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites. Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation. Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone. Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.

Synergistic Antinociceptive Effect of ß-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity.

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since ß-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus ß-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and ß-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of ß-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with ß-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

From Selye's and Szabo's Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities.

We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo's cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists' beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as "mild stress (or)" or "small irritant" counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents' application in lower gastrointestinal tract therapy.

Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Gastroprotective Effects of Oral Glycosaminoglycans with Sodium Alginate in an Indomethacin-Induced Gastric Injury Model in Rats.

The gastrointestinal (GI) mucosal barrier is often exposed to inflammatory and erosive insults, resulting in gastric lesions. Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), chondroitin sulfate (CS), and N-acetylglucosamine (NAG) have shown potential beneficial effects as GI protectants. This study aimed to evaluate the gastroprotective effects of oral GAGs in rats with indomethacin-induced GI lesions. Forty-five Sprague-Dawley rats (8-9 weeks-old, 228 ± 7 g) were included in the study, divided into five study groups, and given, administered orally, either sucralfate (positive control group; PC), NAG (G group), sodium alginate plus HA and CS (AHC group), sodium alginate plus HA, CS, and NAG (AHCG group), or no treatment (negative control group; NC). Animals were administered 12.5 mg/kg indomethacin orally 15 min after receiving the assigned treatment. After 4 h, stomach samples were obtained and used to perform a macroscopic evaluation of gastric lesions and to allow histological assessment of the gastric wall (via H/E staining) and mucous (via PAS staining). The AHCG group showed significant gastroprotective improvements compared to the NC group, and a similar efficacy to the PC group. This combination of sodium alginate with GAGs might, therefore, become a safe and effective alternative to prescription drugs for gastric lesions, such as sucralfate, and have potential usefulness in companion animals.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

Background and aim: In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. Experimental procedure: The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Results and conclusion: Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 µL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

Herbal melanin modulates PGE2 and IL-6 gastroprotective markers through COX-2 and TLR4 signaling in the gastric cancer cell line AGS.

We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) and toll-like receptor 4 (TLR4)-mediated interleukin-6 (IL-6) production and secretion play major roles in gastric mucosal protection. In the current study, the human gastric carcinoma epithelial cell line AGS was used as a model to investigate the effect of HM on TLR4, COX-2, glycoprotein mucin 4 protein and gene expression using immuno-cyto-fluorescence staining, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gastroprotective markers PGE2 and IL-6 production and secretion were also assessed using an enzyme-linked immunosorbent assay (ELISA). Bacterial lipopolysaccharides (LPS), well-known inducers of TLR4, COX-2, PGE2 and IL-6 expression, were used as a positive control. We showed that HM upregulated its main receptor TLR4 gene and protein expression in AGS cells. HM increased, in a dose- and time-dependent manner, the secretion of PGE2 and the expression of COX-2 mRNA and protein, which was detected in the nucleus, cytoplasm and predominantly at the intercellular junctions of the AGS cells. In addition, HM enhanced IL-6 production and secretion, and upregulated the mucin 4 gene expression, the hallmarks of gastroprotection. To check whether HM-induced PGE2 and IL-6 through TLR4 signaling and COX-2 generated, AGS cells were pre-treated with a TLR4 signaling inhibitor TAK242 and the COX-2 inhibitor NS-398. A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.

Úlcera péptica / Peptic ulcer

La enfermedad ulcerosa péptica es una patología frecuente; aunque su incidencia ha disminuido en los últimos años, sigue siendo una causa importante de morbimortalidad asociada a un elevado gasto sanitario. Los factores de riesgo más importantes son la infección por Helicobacter pylori(H. pylori) y el uso de antiinflamatorios no esteroideos. La mayoría de los pacientes con enfermedad ulcerosa péptica permanecen asintomáticos, siendo la clínica más frecuente la dispepsia, a menudo característica (dispepsia ulcerosa). También puede comenzar con complicaciones como hemorragia digestiva alta, perforación o estenosis. La técnica diagnóstica de elección es la endoscopia digestiva alta. El tratamiento con inhibidores de la bomba de protones, la erradicación de H. pylori y evitar el consumo de antiinflamatorios no esteroideos son la base del tratamiento. Sin embargo, la prevención es la mejor estrategia, incluye una adecuada indicación de inhibidores de la bomba de protones, la investigación y tratamiento de H. pylori, evitar los antiinflamatorios no esteroideos o utilizar aquellos menos gastrolesivos (AU)

Peptic ulcer disease is a frequent pathology; although the incidence has decreased in recent years, it continues to be an important cause of morbidity and mortality associated with high healthcare costs. The most important risk factors are Helicobacter pylori(H. pylori) infection and the use of non-steroidal anti-inflammatory drugs. Most patients with peptic ulcer disease remain asymptomatic, with dyspepsia being the most frequent and often characteristic symptom. It can also debut with complications such as upper gastrointestinal bleeding, perforation or stenosis. The diagnostic technique of choice is upper gastrointestinal endoscopy. Treatment with proton pump inhibitors, eradication of H. pylori and avoiding the use of non-steroidal anti-inflammatory drugs are the basis of treatment. However, prevention is the best strategy, it includes an adequate indication of proton pump inhibitors, investigation and treatment of H. pylori, avoiding non-steroidal anti-inflammatory drugs or using those that are less gastrolesive (AU)

In vitro anti-inflammatory activity and ameliorative effects on gastric ulcers of Licania rigida benth seed extract.

Licania rigida Benth., a Brazilian endemic plant, has been traditionally used for treating inflammation and stomach pain. This work investigates the anti-inflammatory and gastroprotective activities of the ethanolic extract from L. rigida seeds (EELr) by in vitro and in vivo methods. The phytochemical profile was determined and the in vitro antioxidant activity was investigated by radical scavenging and thiobarbituric acid reactive substances methods. The ovalbumin denaturation method was used with sodium diclofenac as standard for the in vitro anti-inflammatory activity assessment. Acetylsalicylic acid was used to induce gastric ulcers in male mice and then to evaluate the preventive and therapeutic gastroprotective effect of EELr, using omeprazole as the reference drug. The extract exhibited relevant amount of phenolic compounds and flavonoids, in particular, demonstrating in vitro antioxidant capacity. EELr was able to inhibit almost 60% of ovalbumin denaturation at a concentration considered low. It also prevented the decrease of biochemical markers for oxidative stress such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the stomach and SOD and catalase (CAT) in the liver. EELr also significantly decreased the number of lesions as well as reduced the ulcerated area when used as therapy. The observed effect may be due to its phenolic compounds, such as chlorogenic acid, caffeic acid and tannins, as previously reported. EELr is a potential source of compounds with anti-inflammatory activity, protects the liver from oxidative damage and improves healing of aspirin-induced ulcers. This work contributes to the knowledge of L. rigida species.

[Peptic ulcer]. / Úlcera péptica.

Peptic ulcer disease is a frequent pathology; although the incidence has decreased in recent years, it continues to be an important cause of morbidity and mortality associated with high healthcare costs. The most important risk factors are Helicobacter pylori(H. pylori) infection and the use of non-steroidal anti-inflammatory drugs. Most patients with peptic ulcer disease remain asymptomatic, with dyspepsia being the most frequent and often characteristic symptom. It can also debut with complications such as upper gastrointestinal bleeding, perforation or stenosis. The diagnostic technique of choice is upper gastrointestinal endoscopy. Treatment with proton pump inhibitors, eradication of H. pylori and avoiding the use of non-steroidal anti-inflammatory drugs are the basis of treatment. However, prevention is the best strategy, it includes an adequate indication of proton pump inhibitors, investigation and treatment of H. pylori, avoiding non-steroidal anti-inflammatory drugs or using those that are less gastrolesive.

Metabolites Profiling and Bioassays Reveal Bassia indica Ethanol Extract Protective Effect against Stomach Ulcers Development via HMGB1/TLR-4/NF-κB Pathway.

Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers' progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1ß and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1ß and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI-Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

The nitric oxide-cyclic GMP-KATP channels pathway contributes to the effects of montelukast against gastric damage induced by ethanol.

The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene receptor, and the involvement of the NO-cGMP-KATP channel pathway, were evaluated in gastric damage induced by ethanol in rats. For this, l-arginine, l-NAME, methylene blue (guanylate cyclase inhibitor), sildenafil, diazoxide, or glibenclamide (ATP-sensitive potassium channel blocker) were administered 30 min before montelukast (0.1, 1, 10, and 20 mg/kg, by mouth [p.o.]). After 1 h, to induce gastric damage, the rats received absolute ethanol (4 mL/kg, p.o.), and then microscopic, macroscopic, and pro-inflammatory parameters (TNF-α and IL-1ß) were assessed. Results obtained here revealed that montelukast significantly attenuated the macroscopic and microscopic lesions induced by ethanol. Montelukast also reduced IL-1ß and TNF-α levels. It was also observed that NOS inhibitor (l-NAME), methylene blue, and glibenclamide inhibited the effects of montelukast in the stomach. Moreover, the NO precursor (l-arginine), the PDE-5 inhibitor (sildenafil), and a potassium channel opener (diazoxide) before montelukast produced gastroprotective effects. In conclusion, the effect of montelukast against gastric lesions induced by ethanol is mediated, at least in part, through the pathway of the NO-cGMP-KATP channel.

The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats.

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE2, NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing.

Gastroprotective effect of the crude ethanolic extract from the stem barks of Piptadenia viridiflora (Kunth) Benth. (Fabaceae) / Efecto gastroprotector del extracto etanólico crudo de la corteza de Piptadenia viridiflora (Kunth) Benth. (Fabaceae)

The objective of this work was to evaluate the gastroprotective activity of the crude ethanolic extract (CEE) from the stem barks of Piptadenia viridiflora using the acute models of inducing gastric ulcers by ethanol, ethanol-acidified, and ischemia-reperfusion, and correlating this response with the antioxidant activity, as well as, analyze the chemical profile of the extract by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). For this purpose, mice and rats were used. The ethanol ulcer induction test showed that CEE at doses of 100 and 200 mg/kg promoted 70% and 80% of gastroprotection, respectively. In the gastric ulcer induction test by acidified-ethanol and ischemia-reperfusion, CEE (200 mg/kg) promoted 66% and 90% of gastroprotection in animals, respectively. In conclusion, this species has gastroprotective activity, and this response is possibly related to the antioxidant activity, as well as the presence of flavonoids detected in CEE of P. viridiflora.

El objetivo de este trabajo fue evaluar la actividad gastroprotectora del extracto etanólico crudo (CEE) de Piptadenia viridiflora, utilizando los métodos de inducción de úlceras gástricas agudas por etanol, etanol acidificado y de isquemia-reperfusión, y correlacionando esta respuesta, con la actividad antioxidante, así como, perfil químico de la muestra. Para ello se utilizaron ratones (Swiss) y ratas (Wistar). Como resultado, la prueba de inducción de úlceras por etanol mostró que la CEE a dosis de 100 y 200 mg/kg promovió 70% y 80% de gastroprotección, respectivamente. En la prueba de inducción de úlcera gástrica por etanol acidificado e isquemia-reperfusión, la CEE (200 mg/kg) promovió 66% y 90% de gastroprotección en animales, respectivamente. Concluimos que la especie tiene una acción gastroprotectora y que esta respuesta posiblemente esté relacionada con la actividad antioxidante, así como con la presencia de flavonoides detectados en la CEE de P. viridiflora.

Phenolic acids-rich fraction from Ficus drupacea leaves for the prevention and treatment of ethanol-induced gastric mucosal injury in rats.

Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC-PDA-ESI-MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.

Enhanced Stability of Vegetal Diamine Oxidase with Trehalose and Sucrose as Cryoprotectants: Mechanistic Insights.

Enteric dysfunctions are common for various histamine-related intestinal disorders. Vegetal diamine oxidase (vDAO), an enzyme able to decompose histamine and thus alleviate histamine-related dysfunctions, was formulated in gastro-resistant tablet forms for oral administration as a food supplement and possible therapeutic agent. A major challenge for the use of proteins in the pharmaceutical field is their poor stability. In this study, vDAO was freeze-dried in the absence or in the presence of sucrose or trehalose as cryoprotectants and then formulated as tablets by direct compression. The stability of the obtained preparations was followed during storage at 4 °C and -20 °C for 18 months. In vitro dissolution tests with the vDAO powders formulated as tablets were performed in simulated gastric and in simulated intestinal fluids. The tablets obtained with the powder of the vDAO lyophilized with sucrose or trehalose cryoprotectants offered better protection for enzyme activity. Furthermore, the release of the vDAO lyophilized with the cryoprotectants was around 80% of the total loaded activity (enzyme units) compared to 20% for the control (vDAO powder prepared without cryoprotectants). This report revealed the potential of sucrose and trehalose as cryoprotectants to protect vDAO from freeze-drying stress and during storage, and also to markedly improve the vDAO release performance of tablets obtained with vDAO powders.

Antiulcerogenic and healing activity of hecogenin acetate in rodents.

Peptic ulcers are lesions in the gastric and duodenal mucosa generated by an imbalance between protective factors (gastroduodenal mucus secretion, bicarbonate production, adequate blood flow) and harmful factors (excess pepsin or hydrochloric acid). Some drugs used in peptic ulcer therapy are associated with adverse effects. The aim of this study was to evaluate the antiulcerogenic and healing activity of hecogenin acetate (HA) in acute and chronic models of gastric lesions in rodents. The antiulcerogenic activity of HA was evaluated in models of gastric lesions induced by absolute ethanol and in acidified ethanol with HA (5, 10, and 20 mg/kg). For the model of gastric lesions induced by ischemia and reperfusion, rats were pre-treated with HA (5, 10, 20 mg/kg). After that, they were submitted to 30 min of ischemia, followed by 1 h of reperfusion. To evaluate the healing activity was induced gastric ulcer using acetic acid (80%) in rats. After 24 h, they were treated for 7 consecutive days with HA (10 and 20 mg/kg). They were evaluated the possible signs of toxicity, measurement of the lesions, collagen deposition, and histological analysis. HA significantly reduced the area of the lesion in models of gastric lesions induced by absolute and acidified ethanol, ischemia-induced gastric lesions and reperfusion, and regarding healing. In the collagen deposition, the presence and increase of collagen demonstrate the healing effect. The AH has antiulcerogenic and healing potential demonstrated by the decrease in gastric injury and presence of collagen fibers, respectively.

Use of food and food-derived products in the treatment of gastritis: A systematic review.

Gastritis is the acute or chronic inflammation of gastric mucosa and is triggered by diverse factors. Treatments used for non-bacterial gastritis include proton pump inhibitors, histamine H2 receptor inhibitors, and antacids, and their use is linked to various side effects. Research on alternative therapeutics using food or food-based products is extensive, mostly in preclinical research. We aimed at documenting the clinical advances in food-based therapies as alternative therapeutics for gastritis. Articles with information on the treatment of gastritis with food or food-based products published until December 1, 2020 were identified through a systematic search in PubMed Medline Database. Additionally, references of retrieved articles were screened for relevant reviews and meta-analyses. Two investigators independently selected and reviewed the titles and abstracts of articles and extracted the study characteristics (PICO framework) and key findings. Dual quality assessment and data extraction were performed. We found 28 clinical studies evaluating garlic, turmeric, red peppers, broccoli sprouts, cranberry juice, honey, oils, and probiotics contained in different foods, such as juices, yogurt, and cheese. The existing literature presents a high risk of bias, and results of the same should be evaluated and replicated with precaution; more rigorous clinical studies are lacking.