• 대한한방내과학회지
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• 제34권2호
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• pp.204-214
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• 2013

Objectives : This study was designed to investigate the cellular and molecular mechanisms of anti-inflammatory activity of the water extract of Polygala tenuifolia Willd. (Pt-WE). Methods : Using lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells, we examined inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$). Also, the inhibitory effect of Pt-WE on the activity of activator protein 1 (AP-1) and upstream signaling molecules was evaluated. To assess the protective effect of Pt-WE on hydrochloride/ethanol (HCl/EtOH)-induced gastric ulcer in mice, we compared Pt-WE (200 mg/kg) with ranitidine (50 mg/kg) treated mice's gastric mucosa, based on gross observations. Results : Pt-WE inhibited LPS-induced production of NO, $PGE_2$ in a dose-dependent manner, without causing cytotoxicity. Pt-WE suppressed AP-1 activation by reducing generations of both c-Jun and c-Fos. In addition, Pt-WE inhibited the p-MKK 4/7 (mitogen-activated protein kinase kinase 4/7) and p-JNK (c-Jun N-terminal kinase) 1 in LPS-stimulated RAW264.7 cells. HCl/EtOH-induced gastric ulcer lesions were inhibited by pre-treatment of Pt-WE based on gross observations. In addition, Pt-WE decreased the phosphorylation level of JNK. Conclusions : These results demonstrate that Pt-WE has anti-inflammatory and gastroprotective effects. Thus, Pt-WE may be used widely in treatment of not only neurodegenerative diseases but also inflammatory diseases.

• Biomolecules & Therapeutics
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• 제17권1호
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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 Ginseng Research
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• 제44권4호
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• pp.655-663
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• 2020

Background: Korean Red Ginseng is known to exhibit immune-enhancing and anti-inflammatory properties. The immune-enhancing effects of the nonsaponin fraction (NSF) of Korean Red Ginseng have been studied in many reports. However, the gastroprotective effect of this fraction is not fully understood. In this study, we demonstrate the activities of NSF for gastrointestinal protection and its related critical factor. Methods: The in vitro and in vivo regulatory functions of NSF on cyclooxygenase-1 (COX-1) messenger RNA and protein levels were examined by reverse transcription polymerase chain reaction and immunoblotting analyses. Gastroprotective effects of NSF were investigated by histological score, gastric juice pH, and myeloperoxidase activity on indomethacin-induced, cold stress-induced, and acetylsalicylic acid-induced gastritis and dextran sulfate sodium-induced colitis in in vivo mouse models. Results: NSF did not show cytotoxicity, and it increased COX-1 messenger RNA expression and protein levels in RAW264.7 cells. This upregulation was also observed in colitis and gastritis in vivo models. In addition, NSF treatment in mice ameliorated the symptoms of gastrointestinal inflammation, including histological score, colon length, gastric juice pH, gastric wall thickness, and myeloperoxidase activity. Conclusion: These results suggest that NSF has gastroprotective effects on gastritis and colitis in in vivo mouse models through COX-1 upregulation.

• 한국유기농업학회지
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• 제30권1호
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• pp.75-87
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• 2022

본 연구는 다량 미네랄 6종 및 미량 미네랄 8종이 함유된 천연 미네랄 워터의 기능성을 확인하기 위해 역류성 식도염 유발 동물모델을 이용하여 개선 효과를 분석하였다. RAW264.7에서의 세포 생존율 측정 결과를 통해 미네랄 워터는 세포에 대한 독성이 없음을 확인하였으며, 역류성 식도염 동물모델에서 위 내용물 역류에 의한 식도 손상을 감소시켰으며, 식도 점막 보호 작용으로 인해 세포 연접 단백질 발현을 억제하였다. 따라서, 미네랄 워터의 식도 보호 작용은 조직 내 염증성 단백질 및 점막 재생 관련 단백질을 조절함으로써 나타난 것으로 사료된다. 이러한 연구 결과를 통해, 미네랄 워터의 기능성을 확인함으로써 음용수, 식품 생산 등의 다양한 산업 분야에서의 활용성과 가축 생산에 있어 면역증진 및 염증 관련 질병에 대처할 수 있는 친환경 기능성 사료첨가제로서의 미네랄 워터의 이용 가치를 확인할 수 있었다.

• 생명과학회지
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• 제23권4호
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• pp.602-608
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• 2013

만성적인 염증이 다단계 발암과정에서 다면적인 역할을 하고 있음은 이미 잘 알려진 사실이다. 치주 질환의 원인은 구강 박테리아에서 분비되는 내독소들과 염증 유발인자들의 생성 등이 관여하는 다양한 요인들을 포함하며, 이는 잘못된 구강 위생 관리가 신체의 여러 가지 전신병적 원인과 연관되어 있음을 의미한다. 비위생적인 구강 상태와 연관된 만성 염증, 흡연, 알콜 섭취의 증가 등은 암의 발병 위험 요소로 작용함은 명확한 사실이다. 최근에는 구강 위생과 치아 손실이 위장관암, 폐암 및 췌장암 뿐만 아니라 혈구암 발병 증가와 직접적인 연관성이 있음이 밝혀졌다. 또한 흡연은 악성 질환 발병의 위험 요소로서 구강 위생의 강력한 위해요인임은 명백하며, 역학적 조사결과들에 의하면 구강 박테리아에 의한 치주 질환은 만성 염증을 통하여 흡연과 알콜 연관 발암원을 활성시킴으로서 다양한 암의 발병 위험 요소를 증가시킬 수 있는 것으로 나타났다. 따라서 암 뿐만 아니라 다른 다양한 질환의 예방을 위한 적절한 구강 관리는 필수적이다. 본 논문에서는 암예방을 위한 악성질환의 위해 요소로서 염증과 치주질환 및 구강 위생과의 연관성을 논하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.945-950
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• 2014

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.825-830
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• 1997

Leukotrienes(LTs) are hewn to act as a mediator provoking tissue response in inflammation. This finding implicates that LTs also play important roles in the pathogenesis of H, pylori-induced gastritis and gastric ulceration. Rebamipide is being currently used as a therapeutics for gastritis and peptic ulcer, but their mechanisms of action have not been known clearly yet. One possibility is that their therapeutic effects are ascribed to interfering with the H. pylori-induced release of LTs from neutrophils and gastric mucosal cells. In the present study, this possibility was tested using $LTB_4$ as the test material in human neutrophils and Kato III cells(gastric adenoma cells as a substitute for gastric mucosal cells). The release of $LTB_4$ from both neutrophils and Kato III cells was time and H. pylori-dose dependent. The maximum release of $LTB_4$ was induced by neutrophils and Kato III cells when these cells incubated with H. pylori $(4.8{\times}10^8\;cells/ml$ for 30min. But in the presence of rebamipide the release of $LTB_4$ from these cells was suppressed in dose dependent manners. The release was completely suppressed at 1.0 mM of rebamipide in neutrophils and 2.0 mM of this drug in Kato III cells, respectively. We also obtained the results that the release of $LTB_4$ was induced by A23187$(Ca^{2+}\;ionophore)$ and the A23187-induced release was also inhibited by rebamipide. It seems that the machanism of action of rebamipide is through its interaction with the level of intracellular $Ca^{2+}$. In view of the roles of $LTB_4$ in inflammatory reaction and the roles of H. pylori in gastritis and peptic ulcer, the effects of this drug observed in this study may contribute to their therapeutic action in these gastric disorders.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.196-203
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• 2014

Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. Materials and Methods: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: nonulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제6권1호
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• pp.1-9
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• 2003

목 적: Helicobacter pylori (H. pylori)에 의한 질병 발생의 병독 인자로 cagA, picB 및 iceA 등의 유전형이 연구되고 있으며, 최근에는 위 상피세포의 증식(proliferation)과 세포사(apoptosis)의 불균형이 중요시되고 있다. 이에 H. pylori 감염 소아에서 위 상피세포 증식과 세포사 및 cagA, picB 및 iceA 유전형의 관련성을 알아보고자 하였다. 방 법: 1999년 8월부터 2001년 6월까지 이화여자 대학교 목동병원 소아과에서 소화기 증상으로 내시경을 시행하여 H. pylori 감염으로 진단된 20예와 감염 음성 20예를 대상으로 하였다. H. pylori 감염 양성은 조직학적으로 H. pylori 균이 관찰되고, CLO 검사와 ureC PCR이 전부 양성인 경우로 하였다. 위생검 조직에서 개정된 시드니 체계를 이용하여 조직 소견을 분석하고, proliferating cell nuclear antigen (PCNA) 발현으로 위 상피세포 증식의 정도를 in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) 방법으로 세포사의 정도를 조사하였다. cagA, picB 및 iceA 유전자에 대해 중합효소연쇄반응을 시행하였다. 결 과: 1) 세포 증식 지표는 H. pylori 감염 양성에서 $77.4{\pm}13.12$로 음성 $52.3{\pm}12.20$에 비하여 유의하게 높았다(p=0.000). 세포 증식 지표는 H. pylori 밀도가 증가할수록(r=0.624, p=0.000, 다핵형 중성구의 활동성이 증가할수록(r=0.460, p=0.005), 만성 염증이 증가할수록(r=0.433, p=0.009) 증가하였다. 2) 세포사 지표는 H. pylori 감염 양성에서 $0.70{\pm}0.411$, 음성에서 $0.14{\pm}0.201$로 감염 양성에서 음성보다 유의하게 높았다(p=0.000). 세포사 지표는 H.pylori 밀도가 증가할수록(r=0.691, p=0.000), 다핵형 중성구의 활동성이 증가할수록(r=0.585, p=0.000), 만성 염증이 증가할수록(r=0.535, p=0.001) 증가하였다. 3) 세포 증식 지표가 증가할수록 세포사 지표는 유의하게 증가하였다(r=0.527, p=0.001). 4) H. pylori 감염 양성에서 유전형의 양성률은 cagA 90%, picB 75%, iceA1 60% 및 iceA2 15%였으며, cagA, picB, 및 iceA 유전형에 따른 세포 증식지표, 세포사 지표, 내시경 소견 및 조직 소견에는 유의한 차이가 없었다. 결 론: H. pylori 감염 소아에서 위 상피세포 증식 지표와 세포사 지표가 균형을 이루면서 증가하였으며, cagA, pic B 및 iceA 유전형에 따른 유의한 차이는 없었다. 이는 위 상피세포 증식과 세포사가 H. pylori의 병인에 중요함을 시사하며, 앞으로 세포 증식과 세포사의 기전과 유발 요인, 여러 유전형과의 관계, 성인과의 비교 연구 등이 필요하리라 생각된다.

• 한국식품영양학회지
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• 제23권4호
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• pp.542-548
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• 2010

This study was conducted to investigate the effects of Acanthopanax senticosus extracts(ASE) on alcohol administered mice. The administration of Acanthopanax senticosus extracts(60 mg/kg) had beneficial actions toward alcohol degradation in acute alcohol treated mice. In the acute alcohol degradation experiment, serum alcohol concentration were lower 3 and 6 hours after taking ethanol(5 g/kg) in ASE treated mice. The oral administration of ASE showed decreased gastric mucous membrane damage produced in ethanol treated mice. In addition, intraperitoneal(i.p.) administration of ASE showed antiinflammatory effects in inhibition tests of vascular permeability produced by acetic acid. ASE also reduced concentrations of nitric oxide(NO), tumor necrosis alpha(TNF)-${\alpha}$ and interleukin(IL)-6 in macrophages that were activated by LPS. These results demonstrate that Acanthopanax senticosus extracts possesses the potential to stimulate alcohol degradation and inhibit inflammatory effects in mice.