• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.167-167
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• 2003

Hepatic stellate cells (HSC) and the derived myofibroblasts are known to playa central role in liver fibrosis. 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) on the proliferation, the collagen synthesis, and hepatic fibrosis related proteins mRNA levels in HSC-T6 cells which is a fully acivated rat hepatic stellate cell line.(omitted)

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.243-248
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• 2008

In the present study, we investigated activity change of sphingomyelin anabolic enzymes such as sphingomyelin synthase and ceramide synthase. Sprague-Dawley male rats treated with 10 mg/kg of DMN intraperitoneally were used as a hepatic fibrosis model. Sphingomyelin synthase and ceramide synthase activities were measured in 1-week, 2-week, 3-week and 4-week DMN-treated rats along with respective control group rats. We found the increased sphingomyelin synthase activity in 4-week DMN-treated liver but not in kidney. Ceramide synthase activity was significantly increased in DMN-treated kidney after 2-week treatment and in DMN-treated liver after 3-week treatment. Although further investigation is necessary to elucidate meanings of sphingolipid metabolites during the liver fibrosis, activity change of sphingolipid anabolic enzymes may imply that sphingolipid metabolism and sphingolipid metabolites could be involved in liver fibrosis especially under oxidative stress.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.138-143
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• 2023

Liver fibrosis is caused by metabolic problems such as cholestasis, genetic problems, or viral infections. Inhibiting hepatic stellate cell (HSC) activation or inducing selective apoptosis of activated HSCs is used as a treatment strategy for liver fibrosis. It has been reported that when HSCs are activated, their apoptosis sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is enhanced because the expression of death receptor 5 is elevated. Finding a natural compound that can enhance the apoptotic effect of TRAIL on HSCs is a necessary strategy for liver fibrosis treatment. It was confirmed here that mangosteen-derived gartanin increased the effect of TRAIL-induced apoptosis by increasing the expression of DR5 in a p38-dependent manner in the hepatic stellate cell line LX-2. Combined treatment with gartanin and TRAIL accelerated DNA cleavage through caspase-3 activation and enhanced antifibrotic effects in LX-2 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• 대한의생명과학회지
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• 제23권2호
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• pp.144-153
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• 2017

It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation ($TNF{\alpha}$ and VCAM-1), fibrosis (${\alpha}-SMA$), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes ($TNF{\alpha}$ and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.132-132
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• 2002

Mostly, hypercholesterolemia has been focused on atherosclerosis and coronary heart disease and can be produced by intake of high cholesterol diet. However, toxic effects of cholesterol itself on liver and relationship between intake of high cholesterol diet and hepatic fibrosis have not been clearly investigated. Male Wistar rats were fed diet supplemented with 1.0 ％ cholesterol and 0.3 ％ sodium cholate for 12 weeks. Rats were sacrificed at 0, 3, 6, 9 and 12, respectively. Histopathological and blood chemical studies were performed on these animal sets. Total cholesterol, AST, ALT and LDH levels increased from week 3 and maintained around that level throughout the experiment compared to control. However, TG and albumin levels were the same or lower than those of control. Intake of high cholesterol and sodium cholate diet caused hepatic necrosis, macrophage infiltration, steatosis and fibrosis. Following feeding this diet to rats, hepatic necrosis, macrophage infiltration and steatosis markedly increased throughout the experiment, comparing to control. Collagen deposition and myofibroblasts were detected from at week 9 to 12 in the liver. Mast cell increased in proportion to the degree of hepatic damages. In conclusion, these results suggest that intake of high cholesterol diet is a risk factor on hepatic steatosis and fibrosis as well as atherosclerosis and coronary heart disease. Furthermore, this animal model for hepatic fibrosis can be use for application of anti-fibrogenic agents screening in vivo.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권1호
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• pp.60-64
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• 2008

저자들은 어린 영아기에 선천성 간섬유증으로 진단받은 후 특징적인 얼굴 모습과 함께 발달 및 지능 저하를 보이는 10세 남아에서 가부키 증후군으로 진단된 1예를 경험하였기에 문헌고찰과 보고하는 바이다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.176.1-176.1
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• 2003

The protective effects on hepatic fibrosis of an aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), in hepatic stellate cell line, CFSC-2G. 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. (omitted)

• 대한영상의학회지
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• 제82권1호
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• pp.116-127
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• 2021

목적 간 섬유화 단계 평가를 위한 회색조 초음파 영상 기반 텍스처 분석 측정 변수들의 진단적 유용성에 대해 평가한다. 대상과 방법 간 회색조 초음파 검사를 시행한 총 167명의 환자를 대상으로 하였다. 텍스처 분석은 한 명의 의사가 전용 소프트웨어를 이용하여 시행하였으며 3, 5, 6, 7, 8번 간 분절에 20픽셀에 해당하는 원형 관심 영역을 지정하여 측정하였다. 간 섬유화 정도에 대한 표준 품으로는 fibrosis-4 (이하 FIB-4 index)를 사용하였다. 산출된 텍스처 변수들과 간의 섬유화 정도의 비교는 t-검정과 Mann-Whitney U 검정을 사용하였으며, 진단적으로 유의한 변수들에 대하여 수신자 운영 특성 곡선의 곡선 하 면적(area under the receiver operating characteristic curve)으로 진단능을 평가하였다. 결과 연구에 포함된 환자는 정상군(FIB-4 < 1.45, n = 50), 경도(1.45 ≤ FIB-4 ≤ 2.35, n = 37), 중등도(2.35 < FIB-4 ≤ 3.25, n = 27)와 중증 간 섬유화군(FIB-4 > 3.25, n = 53)으로 구분되었다. 간의 5번 분절에서 왜도는 정상군과 경도군 사이에서 통계적으로 유의한 차이를 보였다(각각 0.2392 ± 0.3361, 0.4134 ± 0.3004, p = 0.0109). 정상군과 경도군을 구별하기 위한 왜도의 곡선 하 면적은 0.660 (95% confidence interval, 0.551-0.758) 이었으며, 추정 정확도, 민감도, 특이도는 각각 64%, 87%, 48%로 산출되었다. 결론 왜도는 5번 간 분절에서 정상군과 경도 섬유화군을 구분하는 데 유의한 차이를 보였다.

• 대한한방내과학회지
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• 제24권1호
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• pp.21-32
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• 2003

Objective : The aim of this study is to investigate the inhibitory effect of Injinchunggantang on hepatic sclerosis induced by $CCl_4$. Methods : Weight, liver function test and complete blood cell count, gross findings, and findings on liver tissue of the past(Hematoxylin & Eosin stain, Masson-Trichrome stain) were studied. Results : When it comes to the change of rats' body weight, The $CCl_{4^+}$Injinchunggantang group lost far less weight than The $CCl_{4^-}$only group. In the liver function test, which is focused on various areas such as total cholesterol, alkaline phosphotase, albumin, aspartate transaminase, alanine transaminase, The $CCl_{4^+}$Injinchunggantang group was much more closer to normal limit than the $CCl_4$ only group. In the complete blood cell count, including white blood cell, red blood cell, hemoglobin, hematocrite, platelet, The $CCl_{4^+}$Injinchunggantang group significantly closer to normal limit than $CCl_{4^-}$only group. In the gross findings of hepatic fibrosis models, Injinchunggantang showed inhibitory effect on hepatic fibrosis in the order. In the past findings of hepatic fibrosis models in Hematoxylin & Eosin, Masson-Trichrome staining, the liver in $CCl_{4^-}$only group showed atrophy and necrotic change with white nodules, whereas that of $CCl_{4^+}$Injinchunggantang group showed lesser significant change with the well_preserved tone of the tissue. In the extent of the inhibition of the hepatic fibrosis, the Injinchunggantang group showed statistically significant inhibitory effect(p<0.05) in the sclerosis model. Conclusions : These results show that Injinchunggantang have inhibitory effect on hepatic sclerosis induced by $CCl_4$ and further ultimately prevent liver cirrhosis. To obtain more credible results in this experiment, the invention of a new experimental model more similar to human hepatic sclerosis is still needed.