• The Korea Journal of Herbology
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• v.33 no.4
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• pp.9-18
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• 2018

Objectives : This study aimed to investigate the anti-ulcer effect of an standardized herbal extracts mixture of Inulae Flos and Paeoniae Radix (HT074) on acidified ethanol induced gastric injury and its potential mechanisms. Methods : Antioxidant activities of HT074 and its constituents were measured by DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging capacity. After the oral administration of HT074 at doses of 100, 300 mg/kg twice per day for 14 days, Gastric lesions were induced by oral administration of acidified ethanol in Sprague Dawley rats. Oxidative stress markers, such as super oxide dismutase (SOD) activity, concentrations of catalase (CAT) and glutathione (GSH) were measured in gastric mucosal tissues. Additionally, the expression of human mucin gene, Mucin 5AC (MUC5AC) mRNA in gastric mucosal tissues was measured. Results : HT074 showed dose dependent radical scavenging activities against DPPH and ABTS radicals. Oral administration of HT074 300 mg/kg for 14 consecutive days significantly decreased gastric lesions and histological damages induced by HCl/EtOH in rats. HT074 treatment significantly increased the activity of SOD (300 mg/kg) and concentration of GSH (100 and 300 mg/kg), however catalase concentration was not significantly increased. MUC5AC mRNA expression was significantly increased by HT074 100, 300 mg/kg treatment. Conclusions : HT074 protects the gastric mucosa from oxidative stress caused by acidified ethanol by increasing the activity of SOD, concentration of GSH and mucin biosynthesis. These findings suggest that HT074 could be an effective candidate for prevention and treatment of gastritis and gastric ulcer.

• 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.

• International Journal of Industrial Entomology and Biomaterials
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• v.35 no.1
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• pp.14-21
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• 2017

Gastric ulcer is a clinical symptom characterized by inflammation of the gastric mucosa. Stress and alcohol consumption have been identified as the major cause of gastric ulcer. However, the effects of silkworms on ethanol-induced gastric ulcer have not been studied yet. The mature silkworms that are difficult to eat have become easier to ingest due to recent technological development to make steaming and freeze-drying mature silkworm larval powder (SMSP). In this study, we investigated whether three silkworm varieties, Baekokjam, Golden-silk and Yeonnokjam could alleviate ethanol-induced gastric mucosal damage in vivo. Sprague-Dawley rats pretreated with 3 SMSPs (0.1 or 1 g/kg BW) or normal diet (AIN-76A) were exposed to absolute ethanol (3 g/kg BW, 3 h) by oral gavage. Morphological examination included ulcer index as a measurement of hemorrhages and hematoxylin and eosin staining was performed to analyze the severity of gastric ulcer. Results of macroscopic examination suggested that all 3 SMSPs pretreatment significantly protected gastric mucosa against ethanol-induced damage. Microscopic observations demonstrated significant mucosal erosion and inflammation in ethanol-treated rats, which was abrogated in rats pretreated with 3 SMSPs. In addition, pretreatment with all 3 SMSPs showed significant decreases the expression of pro-inflammatory mediators, IL-6 and cyclooxygenase-2. Among SMSP from 3 varieties of silkworm, preadministration of 1 g/kg Baekokjam SMSP showed the most effective protective effect against ethanol-induced gastric ulcer. These results suggest that Baekokjam SMSP can be a potential gastroprotective agent against ethanol-induced gastric ulcer.

• 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.

• Biomolecules & Therapeutics
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• v.7 no.4
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• pp.362-370
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• 1999

Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents(wax, flavonoids, phenolic compounds, etc.) and has been used in traditional medicines as early as 300 B.C. It was been demonstrated that ethanol, acetylsalicylic acid, ischemia reperfusion, non-steroidal antiin-flammatory drugs and stress induce gastric lesions by promoting the generation of reactive oxygen metabolites. Therefore, some drugs that are capable of scavenging or inhibiting the generation of reactive oxygen radicals might be expected to prevent the gastric mucosal injury. The aim of this study was 1) to examine the antiulcer effect of propolis, 2) to investigate the mechanism of action by determining gastric acid secretion, lipid per-oxidation, mucus content and proton pump ($H^+$/$K^+$-ATPase) activity on gastric mucus in varios experimental models, and finally, 3) to isolate and identify the pure compounds that exert antiulcer activity. Step 2-1 and 2-3 sub-sub fraction shoed a significant reduction of severity of gastirc damage at the dose of 25 mg/kg in various experimental models. We isolated 4 sub-sub-sub fractions by flash column chromatography of Step 2-1 sub-sub fraction and one sub-sub-sub fraction by recrystalization of Step 2-3 sub-sub fraction. The protective effects of propolis sub-sub-sub fraction manifested sifnificant effects in HCl-ethanol induced gastric erosion model and aspirin induced gastric ulcer model. These results showed that the gastric mucosal protective effect of propolis might result from the increase of mucus secretion, free radical scavenging effect as well as the reduction of acid secretion in accordance with the reduction of $H^+$/$K^+$-ATPase activitv. Three compounds were isolated and identified from sub-sub fraction of propolis which showed antiulcer effects. Subsequently, these compounds were identified as a flavonoid, namely, 2-acetoxy-5,7,-dihydroxy-flavanone, galangin and chrysin.

• Korean Journal of Bronchoesophagology
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• v.16 no.2
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• pp.83-90
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• 2010

The pathophysiology of Gastroesophageal reflux disease (GERD) has been known that it is developed when the offense-primarily the gastric acid-pepsin content of the refluxate-overcomes a 3-tiered esophageal protective defense. consisting of antireflux mechanisms, luminal clearance mechanisms, and tissue resistance. Laryngopharyngeal reflux (LPR), which is known as an extraesophageal variant of GERD, has been considered to be developed by transient lower esophageal sphincter relaxation (TLESR), direct mucosal injury by gastric contents, more sensitive mucosa compared to esophagus, and absence of buffering effect and aggravation of the injury due to pepsin. However, hypothesis of the pathophysiology in both entities are numerous and still lack of understanding for being a theory. There is no conflict that understanding the pathophysiology is necessary for resolving the problems of these diseases and numerous studies and results have been releasing. This review could provide clinicians dealing with GERD and LPR with applicable new information and help for overcoming the clinical obstruction.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.511-519
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• 1998

This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and $N^G-nitro-L-arginine$ methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, $N^G-nitro-$ L- arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.188-199
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• 2002

Objectives : Banhasasim-tang has been clinically used to treat upper gastric intestinal discomfort. The object of this study is to examine the defense effect of Banhasasim-tang for acute duodenal injury of the mouse. Methods and Materials : Twenty-one rats were divided into 3 groups and treated as follows: the control group was untreated mice. The ADE group was acute duodenal-damage-elicited mice. The BST group was Banhasasim-tang treated mice before acute duodenal damage elicitation. The groups were examined with common morphology, paneth cells in intestinal crypt, absorptive cells and goblet cells in epithelium, cell division in mucose, COX-l as mucosal protector, COX-2 (which appears to play an important role in inflammation), IL-2R-inducing cellular immuno-chainreaction, and the distribution of apoptotic cells. Results : 1. Common morphology: the ADE group was observed with duodenal injury - loss of villi, infiltration of cells concerned to inflammation (lymphocytes, granular leukocytes) to submucosal layer - by hemorrhagic erosions, while the BST group was seen the same as normal in proportion to increasing treatment time before injury. 2. Histochemical change: the ADE group was observed with noticeable decreased distribution of absorptive cells with microvilli, acid mucin secreted goblet cell, neutral mucin secreted goblet cell, paneth cells compared to the normal group. The BST group was seen to have distribution of epithelium cells resembling normal in proportion to increasing treatment time before injury. 3. Imnunohistochemical change: the ADE group showed a change of factors leading to duodenal injury as reduce of cytokinesis, COX-1, increase of COX-2, IL-2R-. In contrast, the BST group tended to reduction of cytokinesis, COX-1, increase of COX-2, IL-2R- in proportion to increasing taking time before injury. 4. Apoptosis change: the ADE group showed increasing apoptosis cells, in contrast to the BST group which was the same as normal in proportion to increasing treatment time before injury. Conclusions : According to the above results, by increasing the defense system of mucosal epithelium, Banhasasim-tang is thought to effectively protect tissue against ulcers resulting from acute duodenal injury.

• Current Research on Agriculture and Life Sciences
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• v.1
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• pp.201-214
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• 1983

A study was undertaken on rats in order to clarify the gastric mucosal, morphologic response to oral and subcutaneous administration of acetylsalicylic acid(aspirin). Aspirin was administered orally (oral group) and subcutaneously (subcutaneous group) at does rate of 60 mg per kg of body weight per day to 40 normal rats. On the 1st, 3rd, 7th, and 15th day of administration, in addition to clinical observation, 5 rats each from the both groups were sacrificed and examined macroscopically, histologically and electron-microscopically for the morphological changes of gastric mucosal cells with the following results. Although the clinical, macroscopic and histological changes were not significant, marked ultrastructural changes were observed. Parietal and chief cells were affected most severely by the administration of aspirin ; parietal cells showed increase in the number of SER and intracellular canaliculi, where-as in chief cells fragmentation, luminal dilatation, decrease in the number and structural abnormalities of RER were seen. Relatively mild changes were observed in mucous, mucous neck and basal-granulated cells. Although the degree of changes was milder than those of oral group, the similar changes were also observed in the subcutaneous group. From these results, it would be concluded that aspirin injury of gastric mucosa is effected not only by the direct injury to the mucosa but also indirectly by the blood concentration of aspirin.

• 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.