Protective effect of proteins extracted from Plumeria pudica latex on ethanol-induced gastric injury in mice.

Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E(2) (PGE(2)) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE(2) and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE(2) expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE(2) expression.

Protective effect of rosmarinic acid-rich trichodesma khasianum clarke leaves against ethanol-induced gastric mucosal injury in vitro and in vivo

Protective Role of Adiponectin Against Ethanol Induced Gastric Injury in Mice

This study evaluated the protective effects of inhibiting caspase-1 activity or gastric acid secretion on acute gastric injury in mice. AC-YVAD-CMK, omeprazole, or vehicle were administered to mice before cold-restraint stress- or ethanol-induced gastric injury. Survival rates and histological evidence of gastric injury of mice pretreated with AC-YVAD-CMK or omeprazole, and exposed to cold-restraint stress, improved significantly relative to the vehicle group. The increased levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18 following cold-stress injury were decreased by AC-YVAD-CMK, but not omeprazole, pretreatment. The increased expression of CD68 in gastric tissues was inhibited significantly by AC-YVAD-CMK pretreatment. Inhibiting caspase-1 activity in the NLRP3 inflammasome decreased gastric cell apoptosis, and the expression of Bax and cleaved caspase-3. AC-YVAD-CMK pretreatment significantly inhibited cold-restraint stress-induced increases in the expression of phosphorylated IκB-alpha and P38. General anatomy and histological results showed the protective effect of AC-YVAD-CMK on ethanol-induced acute gastric injury. Overall, our results showed that the caspase-1 inhibitor AC-YVAD-CMK protected against acute gastric injury in mice by affecting the NLRP3 inflammasome and attenuating inflammatory processes and apoptosis. This was similar to the mechanism associated with NF-κB and P38 mitogen-activated protein kinase signalling pathways.

Hericium erinaceus (HE) is an edible and medicinal mushroom traditionally used for the treatment of gastric injury in clinical practice. However, scientific evidence of its pharmacological activities has not yet been revealed. This study was designed to investigate the therapeutic effect of HE mycelia in submerged culture on ethanol-induced chronic gastric injury (ECGI) in mice. Gastric injury model was induced by ethanol with chronic and binge ethanol feeding in mice, and then mice were treated with HE mycelia. The stomachs were removed for histopathological examination and inflammatory cytokines measurement. Meanwhile, total proteins of gastric tissue were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling analysis to quantitatively identify differentially expressed proteins (DEPs) in three groups of animals. Bioinformatics analysis of DEPs was conducted through clustering analysis, Venn analysis, Gene Ontology (GO) annotation enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment. The histopathologic characteristics and biochemical data showed that HE mycelia (0.5 and 1.0 g/kg) exhibited therapeutic effects on the ECGI mice. Based on the results of iTRAQ analysis, a total of 308 proteins were differentially expressed in the ethanol group when compared with the control group; 205 DEPs in the high dose of HE (HEH) group when compared with control group; and 230 DEPs in HE group (1.0 g/kg) when compared with ethanol group. KEGG analysis showed that the p53 signaling pathway was closely related to the therapeutic effect of HE mycelia on ECGI. Furthermore, the expression levels of several DEPs, including keratin (KRT) 16, KRT6b and transglutaminase E (TGE), were verified by quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, H. erinaceus mycelia could relieve ethanol-induced chronic gastric injury in mice by ameliorating inflammation as well as regulating epidermal differentiation.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1β, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide. Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion.

Protective effects of genipin on ethanol-induced acute gastric injury in mice by inhibiting NLRP3 inflammasome activation

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats

Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice

The study investigated the protective effect of walnut oligopeptides (WOPs) against ethanol-induced gastric injury using Sprague-Dawley (SD) rats. Rats were randomly divided into seven groups based on body weight (10/group), normal group, ethanol group, whey protein group (220 mg/kg body weight), omeprazole group (20 mg/kg body weight), and three WOPs groups (220, 440, 880 mg/kg body weight). After 30 days of treatment with WOPs, rats were given 5 mL/kg absolute ethanol by gavage to induce gastric mucosal injury. Gastric ulcer index (GUI) were determined and the following measured; gastric content pH, gastric mucin, endogenous pepsinogens (PG), prostaglandin E2 (PGE2), inflammatory cytokines, oxidative stress indicators, and the expression of apoptosis-related proteins were measured to evaluate the gastroprotective effect of WOPs. The results showed that the administration with WOPs markedly mitigated the hemorrhagic gastric lesions caused by ethanol in rats, and decreased the GUI, the gastric content pH, PG1, PG2, and NO levels, enhanced mucin and PGE2. Also, WOPs repressed gastric inflammation through the reduction of TNF-α, IL-6, IL-1β and increase IL-10 levels, and revealed antioxidant properties with the enhancement of superoxide dismutase, glutathione, and catalase activity, while reduction of malondialdehyde. Moreover, WOPs treatment significantly down-regulated Bax, caspase-3 and nuclear factor-κB p65 (NF-κB p65) expression, while up-regulating the expression of Bcl-2 and inhibitor kappa Bα (IκBα) protein. These results indicated that WOPs have protective effects against ethanol-induced gastric mucosal injury in rats through anti-inflammatory, anti-oxidation, and anti-apoptosis mechanisms.

In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α and IL-1β. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug.

BackgroundBanhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats.MethodsGastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline.ResultsBCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg.ConclusionsThese results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.

Liupao tea is a traditional Chinese tea drink. The preventive effect of crude polyphenols in Liupao tea on HCl/ethanol-induced gastric injury was investigated in this study. After a model of gastric injury in mice was established, mouse serum and tissues were analyzed by biochemical and molecular biological methods. The results showed that Liupao tea polyphenols (LTPs) could effectively reduce the area of gastric mucosal lesions, decrease the volume of gastric juice, and increase the pH of gastric juice in mice with gastric injury. Observations of the pathology revealed that LTPs could alleviate cell necrosis and gastric mucosal injury in mice with gastric injury. The SOD activity and GSH level were decreased in mice after gastric injury, while the level of MDA was increased. LTPs could inhibit the changes caused by gastric injury and make the SOD activity, GSH, and MDA levels close to the normal levels. In addition, LTPs could upregulate the mRNA expression of Cu/Zn-SOD, Mn-SOD, CAT, nNOS, and eNOS and downregulate the expression of iNOS in the gastric tissue of mice with gastric injury. Therefore, LTPs can effectively prevent HCl/ethanol-induced gastric injury. HPLC analysis showed that LTP contains six bioactive substances of gallic acid, catechin, caffeine, epicatechin, epigallocatechin gallate, and epicatechin gallate, so the effect of LTP might mainly come from these six components. The effect of a high concentration of LTP is similar to that of ranitidine. LTPs represent a kind of active substance with a protective effect on gastric tissue.