• Archives of Pharmacal Research
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• v.20 no.5
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• pp.414-419
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• 1997

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.279-285
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• 2001

Although only a minority of the infected individuals develops atrophic gastritis and the malignancy, factors governing clinical outcomes subsequent to Helicobacter pylori (H. pylori) infection have not yet been defined. H. pylori infection is characterized by extensive infiltration of neutrophils. Myeloperoxidase (MPO) in neutrophils amplifies the oxidative potential of hydrogen peroxides that induce gastric mucosal damage, thus MPO is suspected to play a role in H. pylori-induced gastric injury. Therefore, we explored the association of host MPO genetic polymorphism with atrophic gastritis upon H. pylori infection. Biopsy specimens taken from the gastric mucosa were examined histologically in 87 patients. The PCR-RFLP assay was used to characterize MPO genotypes. The distributions of MPO genotypes were MPO (G/G) 82% and MPO (G/A) 18%. None of MPO (A/A) genotype was observed. A strong positive correlation between the levels of neutrophil infiltration and gastric atrophy found only in MPO (G/G) but not in MPO (G/A) genotype. These results suggest that MPO genotype is a critical determinant in the pathogenesis of atrophic gastritis subsequent to H. pylori infection. Further works need to clarify the functional relevance of MPO genetic polymorphisms on gastric cell injury.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.85-92
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• 2016

Objectives： This study is experimental comparison of brown rice (BR) and germinated brown rice (GBR) on upper gastrointestinal diseases animal models.Methods： The ICR mice were divided randomly into four groups of six animals each (Normal mice, gastritis mice, gastritis mice treated with BR, gastritis mice treated with 48h GBR). Gastritis was induced by administration of 0.5 mL 150 mM HCl-60% ethanol. Six-week-old male Sprague-Dawley (SD) rats were randomly divided into 7 groups after 1 week adaptation. (Normal rat, reflux esophagitis (RE) rat, RE rat treated with BR, RE rat treated with 24,30,36,48h GBR). Reflux esophagitis was induced by ligation with a 2-0 silk thread both the pylorus and the transitional junction between the forestomach and the corpus in SD rats.Results： HCl/ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of 48h GBR than BR. Optical changes such as hyperemia and multiple erosions were observed in the rats with RE and damage to the normal rats was not apparent. The oral administration of GBR significantly diminished against gross mucosal damage in a germination time-dependent manner. Also, the administration of GBR suppressed the biomarker of oxidative stress, reactive oxygen species (ROS) and produces peroxynitrite (ONOO-) in serum. However, the administration of GBR could not affect to the pH level secreted from stomach when compared with Control group.Conclusions： These findings suggest that GBR could have improving effects on upper gastrointestinal diseases in a germination time-dependent manner.

• The Journal of Korean Medicine
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• v.42 no.4
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• pp.150-163
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• 2021

Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion. Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2'-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulation Results: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE. Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.63-68
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• 2015

Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice.Methods : The ICR mice were divided randomly into five groups of six animals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg).Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO^-) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κB) and inhibitor of phosphorylation of nuclear factor kappa B (p-IκB) were down-regulated in LCE-administrated gastric lesion mice.Conclusions : Our discovery supports that the therapeutic activity of LCE ameliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.11-14
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• 1997

This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by ${\beta}-cyclodextrin$ complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 mg/kg and 68 mg/kg of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation$(DS-{\beta}-CD)$] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that $DS-{\beta}-CD$ was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for $DS-{\beta}-CD$, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that $DS-{\beta}-CD$ exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, $DS-{\beta}-CD$ appears to be less gastrolesive than the standard DS formulation.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.57-61
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• 2009

This study examined whether or not a pretreatment with dehydroepiandrosterone (DHEA) has an effect on indomethacin-induced gastric mucosal damage. The DHEA group, male Sprague-Dawley rats, was administrated with DHEA orally at a dose of 4 mg/day for one week before inducing gastritis with indomethacin (50 mg/kg, p.o.). Histological assay, lipid peroxidation assay, superoxide dismutase (SOD), glutathione peroxidase (GPx) and Catalase activities were determined. Interestingly, it was found that the DHEA pretreatment attenuated the gastric lesion area induced by indomethacin. Rather, the pretreatment with high dose of DHEA led to submucosal edema, leukocyte infiltration in submucosa and mucosal necrosis. The levels of MDA in the DHEA pretreatment were also higher than those in the rats given with vehicle pretreatment. This suggests that the DHEA pretreatment deteriorates severe inflammation in indomethacin-induced gastritis. DHEA supplementation significantly increased SOD activity in the gastric mucosa. However, the catalase and GPx activities were not altered by DHEA. The co-administration of DHEA with an indomethacin might not offer a protective effect against the acute gastritis induced by indomethacin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.970-975
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• 2010

Because Lonicerae Flos has effects of antiinflammatory and antioxidant, we studied an effect of Lonicerae Flos on reflux esophagitis (RE) through those effects. Rats were treated with three different dosages of LF (500, 250 and 125 mg/kg) orally for 14 days before pylorus and forestomach ligation. Six hrs after pylorus and forestomach ligation, we dissected a stomach and examined a stomach volume, gastric acid output, pepsin release in the stomach, total hexose, sialic acid in stomach tissue and histamine contents of sera. The results were compared with an ${\alpha}$-tocopherol (once orally, 1hr before operation, 30 mg/kg) treated group in which the effects on RE were already confirmed. Lonicerae Flos extract (LE) reduced gastric volumes compared to RE control. This indicate that LE protect a stomach mucosa by depressing of gastric acid release and corresponse with a reducing histamine content of serum. And LE decreasd a volume of pepsin in stomach compraed to RE control, LE increased contents of total hexose and sialic acid based on esophageal and gastric mucus. This indicated that an increased mucus by LE protected inflammation of esophagus mucosa and gastric mucosa induced by gastric acid. So, LE suppressed a gasric acid by decreasing a pepsin release in stomach, suppressed an injury of esophagus inducted by gastric acid with increasing esophageal mucus and a minimum dose of LE to RE was 250 mg/kg. The results suggest that antioxidant effects of LF could attenuate the severity of reflux esophagitis and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.

• Journal of Life Science
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• v.33 no.11
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• pp.923-935
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• 2023

Rubus crataegifolius (RC), Ulmus macrocarpa (UM), and Gardenia jasminoides (GJ) are well-known folk medicines in Asia used to treat various gastrointestinal disturbances. The present study evaluated the gastroprotective effect of LS-RUG-com, a mixture of commercially prepared powders of RC, UM, and GJ with a ratio of 3:1:2(w/w/w) against HCl/ethanol-induced gastritis, indomethacin-induced ulcers, and esophageal reflux-induced esophageal mucosal damage and Helicobacter pylori infections. In addition, TNF-α and IL-1β expressions were also determined and measured in esophageal tissue. As to HCl/ethanol-induced gastritis, the LS-RUG-com treatment at a dose of 150 mg/kg showed a remarkable anti-gastritis effect. Regarding indomethacin-induced gastric ulcers, the LS-RUG-com treatment had a significant anti-gastric ulcer effect. Furthermore, in the gastroesophageal reflux disease (GERD) model experiment, the LS-RUG-com treatment resulted in the histological recovery of stomach damage and mucosal injuries. Furthermore, the LS-RUG-com treatment led to an increase in gastric content pH, an increase in mucus protection, and a decrease in gastric pepsin output with a significant decrease in TNF-α and IL-1β. As to the Helicobacter pylori infected animal model, LS-RUG-com had a notable inhibitory effect on Helicobacter growth. The use of RC, UM, or GJ in isolation or the LS-RUG-com treatment as whole had good effects in terms of anti-oxidation, anti-neutralization, gastric acid secretion inhibition, and anti-lipid peroxidation, which supported the use of natural products as systemic gastric protective agents. Our results suggest that the LS-RUG-com might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection from gastric disturbances and related damage.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.149-155
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• 2004

Purpose: According to the recent studies, it is shown that the polymorphism of Interleukin $1\beta$ gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin $1\beta$ is a cytokine markedly inhibiting gastric acid secretion. Interleukin $1\beta$ production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin $1\beta$ gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin $1\beta$ in gastric cancer patients. Materials and Methods: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. Results: T/T genotype at -511 portion was $19.3\%$ in gastric cancer cases and $10\%$ in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 ($1.26\∼18.77$) in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was $27.6\%$ in group with Helicobacter pylori infection and $12.8\%$ in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 ($1.81\~12.81$) in group which had C/C genotype. Conclusion: T genotype at -511 portion among the Interleukin $1\beta$ genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.