• 동의생리병리학회지
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• 제22권4호
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• pp.863-870
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• 2008

The aim of this study was to investigate that Injinoryung-san-Ga-Samchilgun(IJORS) has an inhibitory effect on the development of liver fibrosis in rats. The influence of IJORS on liver stellate cell viability in rat was measured by the MTT assay, and proliferation was measured by the BrdU assay. The mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$, TIMP1, and TIMP2 all of which are associated with liver fibrosis, were analyzed by RT-PCR. The inhibitory effect of IJORS on procollagen production in hepatic stellate cell was examined using by enzyme immuno assay(procollagen Type 1 C-Peptide EIA). And after IJORS was orally administered to experimental rats with thioacetamide(TAA)-induced liver fibrosis for 4 weeks, the body weight, liver function test, complete blood and the change of portal pressure were measured. IJORS prevented hepatic stellate cell viability and proliferation in a dose-dependent manner. IJORS reduced the mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$ and TIMP1 and the production of procollagen protein. IJORS inhibited the increase of AST, ALT, WBC and portal pressure in rats administered by TAA. IJORS is considered to prevent liver fibrosis by inhibiting the activation of stellate cell and production of procollagen and prevent the progress of liver fibrosis by inhibiting the inflammation of liver tissue complicated in many liver disease.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.113.3-114
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• 2003

The increased deposition of extracellular matrix by hepatic stellate cells following liver injury in a process known as activation is considered a key mechanism for increased collagen content of liver during the development of liver fibrosis. In this study, we investigated the protective effects of an aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), on hepatic fibrosis in hepatic stellate cells. We report that CK reduces the accumulation of collagen in acetaldehyde-induced hepatic stellate cells. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.238.1-238.1
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• 2003

Hepatic stellate cells (HSC) and the derived myofibroblasts are known to play a central role in liver fibrogenesis. Rhus verniciflua Strokes (RVS) has traditionally been used in Korea herbal medicine for a stomachic tonic. In this study, we observed the effect of RVS acetone extract (Ra) and its five major components on the proliferation, the collagen synthesis, and hepatic fibrosis related proteins mRNA levels in HSC-T6 cells which is a fully activated rat hepatic stellate cell line. Ra inhibited the proliferation and decreased the content of collagen in the HSC-T6 cells. (omitted)

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.146-146
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• 2002

Hepatic disease has been noted and reported for involvement various detrimental factors. Among many detrimental injury factors, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study is to develop animal model for hepatic fibrosis in pig with ethanol, and to search new anti-fibrogenic agent. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with ceramic water only, ceramic water + liquid diet containing 20％ ethanol and normal tap water + containing 20％ ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, comparing to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate necrosis were evident in the tap water + ethanol fed group 3. However, ceramic water intake group 1 showed normal. Moreover, in group 3, little fatty changes and mild necrosis were observed. Collagen fibers were detected in the spaces of surrounding periportal and interlobular areas in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts was markedly reduced in the group 2 of ceramic water + ethanol. In immunohistochemistry, myofibroblasts were detected in the ethanol and tap water treated group 3. No or a few myofibroblasts were observed in groups 1 and 2. CYP 2E1 was rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP 2E1 in the area of pericentral, while CYP 2E1 was significantly activated in group 3 fed tap and ethanol. Taken together above, alcohol fibrosis model in pig was established. Furthermore, ceramic water had an inhibitory and protecting ability for alcohol-induced hepatic damages.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권2호
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• pp.185-193
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• 1999

목 적: 답즙 정체를 주 소견으로 하는 만성 간질환의 대부분에서 담소관의 증식과 간섬유화가 관찰된다. 특히 간외 담도 폐쇄증에서 가장 현저하다. 그러나 섬유화의 병인에 대해서는 아직까지 많은 논란이 제기되고 있다. 총담관 결찰 후 시간이 경과함에 따른 담소관의 증식과 간섬유화의 진행과정 및 간섬유화에 대한 Ito 세포의 역할을 형태학적으로 조사하고자 본 연구를 하였다. 방 법: 건강한 Sprague-Dawley계 수컷 흰쥐를 대상으로 총담관을 결찰한 후 15일, 21일, 24일, 28일째에 도살하여 담소관의 증식과 간 섬유화의 진행과정을 smooth muscle actin에 대한 면역조직화학적 염색과 전자현미경적 검사를 하였다. 결 과: 1) 총담관 결찰후 시간이 경과할수록 간문맥 중심으로 담소관의 증식과 결체조직의 증식이 증가하였다. 2) 면역조직화학적 검색에서 활성화된 Ito 세포는 smooth muscle actin에 양성반응을 보였고, 총담관 결찰후 시간이 경과할수록 담소관주위와 동모양혈관 주의에서 많이 관찰되었다. 3) 전자현미경적 관찰에서 총담관결찰 후 시간이 경과함에 따라 Ito 세포가 증가하였으며, 지방적의 수가 감소한 근섬유모 세포를 닮은 Ito 세포와 근섬유모 세포의 수가 증가하였다. 결 론: 총담관 결찰후에 볼 수있는 간 섬유화는 활성화된 Ito 세포의 증가와 Ito 세포가 교원질을 분비하는 근섬유 모세포로 변형되기 때문에 생긴 것으로 생각된다.

• 한국임상수의학회지
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• 제28권6호
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• pp.617-620
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• 2011

6개월령 아마존 앵무새(orange winged Amazon parrot, Amazona amazonica)가 2달 간 지속된 체중저하, 식욕감퇴, 복부팽만을 검사 받기 위하여 내원하였다. 신체 검사와 실험실 검사에서 유출성 복수, 아스파라진산 아미노전이효소와 담즙산의 증가 및 알부민-글로불린 비율의 감소와 같은 간부전이 의심되는 소견을 보여주었다. 간 생검을 통하여 담관 비대를 동반한 간섬유화가 진단되었다. 이 증상의 원인은 확실하지 않지만, 간독소에 의한 것으로 여겨진다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권4호
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• pp.333-339
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• 2014

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

• 대한임상검사과학회지
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• 제43권3호
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• pp.113-119
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• 2011

This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

• Biomolecules & Therapeutics
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• 제28권6호
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• pp.527-536
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• 2020

Liver fibrosis constitutes a significant health problem worldwide due to its rapidly increasing prevalence and the absence of specific and effective treatments. Growing evidence suggests that apoptosis-signal regulating kinase 1 (ASK1) is activated in oxidative stress, which causes hepatic inflammation and apoptosis, leading to liver fibrogenesis through a mitogen-activated protein kinase (MAPK) downstream signals. In this study, we investigated whether selonsertib, a selective inhibitor of ASK1, shows therapeutic efficacy for liver fibrosis, and elucidated its mechanism of action in vivo and in vitro. As a result, selonsertib strongly suppressed the growth and proliferation of hepatic stellate cells (HSCs) and induced apoptosis by increasing Annexin V and TUNEL-positive cells. We also observed that selonsertib inhibited the ASK1/MAPK pathway, including p38 and c-Jun N-terminal kinase (JNK) in HSCs. Interestingly, dimethylnitrosamine (DMN)-induced liver fibrosis was significantly alleviated by selonsertib treatment in rats. Furthermore, selonsertib reduced collagen deposition and the expression of extracellular components such as α-smooth muscle actin (α-SMA), fibronectin, and collagen type I in vitro and in vivo. Taken together, selonsertib suppressed fibrotic response such as HSC proliferation and extracellular matrix components by blocking the ASK1/MAPK pathway. Therefore, we suggest that selonsertib may be an effective therapeutic drug for ameliorating liver fibrosis.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.288.2-288.2
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• 2002

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. We previously reported that aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK). had hepatoprotective effects against acetaminophen induced liver injury. In the present study, we assayed the preventive and therapeutic effects of CK on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. (omitted)