• Journal of Ginseng Research
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• 제43권4호
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• pp.606-617
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• 2019

Background: The Panax ginseng berry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processed P. ginseng berry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated. Methods: In this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery. Results: The MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery-operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways. Conclusion: UGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.

• 약학회지
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• 제51권1호
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• pp.7-12
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• 2007

Hepatic cirrhosis is an important feature of chronic liver disease. Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic disease. The antifibrotic effects on liver cirrhosis by oriental herbs extraction material were examined in bile duct ligated rats. Oriental herbs extraction (0.99 mg/kg rat weight/day) was administrated to cirrohotic rats for 4 weeks. Liver collagen content of bile duct ligated rats was significantly increased. And liver histology showed collagen fiber deposition was increased as well as the normal architecture was lost with large zone of necrosis being observed. Herbs extraction administrated rats showed significantly decreased liver collagen content, accumulation of collagen fiber in histological analysis, and biochemical markers of hepatic diseases. Those results demonstrate the usefulness of herbs extraction materials as an antifibrotic agent for liver cirrhosis.

• 대한한의학회지
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• 제18권1호
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• pp.480-498
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• 1997

간경변(肝硬變)은 간장손상(肝腸損傷)을 주로 나타내는 만성(慢性) 전신성(全身性) 질환(疾患)이다. 이것은 각종 병인(病因)이 지속적(持續的) 또는 반복적(反復的)으로 간조직(肝組織)에 작용하여 간세포(肝細胞)의 변성(變成) 괴사(壞死) 섬유성(纖維性) 조직(組織) 증식(增殖) 등의 병리변화(病理變化)를 일으켜 결국 간조직(肝組織)의 정상구조(正常構造)가 변하여 간(肝)의 형태이상(形態異常)과 경화(硬化)를 유발하는 것이다. 한의학(韓醫學)에서는 간경변(肝硬變)의 단계에 따라 표현이 다른데 협통(脇痛), 복창(腹脹), 황달(黃疸), 적취(積聚), 창(脹), 단복창(單腹脹), 수(水), 석수(石水), 간수(肝水)의 범주(範疇)에 해당된다. 울증(鬱症)은 정지부서(情志不舒), 기기울결(氣機鬱結)로 울체(鬱滯)하고 발월(發越)하지 못하여 발생하는 병증(病症)으로, 기울(氣鬱)은 기체혈어성(氣滯血瘀性) 병변(病變)인 적취(積聚)의 전단계(前段階)로 설명되고, 간경변(肝硬變)의 초기상태(初期狀態)에서 나타나는 증상(症狀)들과 유사하다고 볼 수 있으므로, 본(本) 연구(硏究)에 사용된 목향조기산(木香調氣散)과 해울조위탕(解鬱調胃湯)은 기울(氣鬱)에 적용되는 처방(處方)으로서 초기(初期) 간경변(肝硬變)의 섬유화(纖維化) 진행억제(進行抑制)에도 유효할 것으로 사료(思料)된다. 이에 본 연구에서는 담도결찰술(膽道結紮術) 및 Dimethylnitrosamine으로 만성간염(慢性肝炎) 및 간경변증(肝硬變症)을 유발한 후 목향조기산(木香調氣散)과 해울조위탕(解鬱調胃湯)을 투여한 결과 다음과 같은 결론을 얻었다. 1. 담도결찰(膽道結紮)로 인한 혈청(血淸) total bilirubin과 direct bilirubin의 상승은 목향조기산(木香調氣散)과 해울조위탕(解鬱調胃湯)의 투여로 모두 억제되는 효과를 보였으며 두 처방(處方)간의 차이는 보이지 않았다. 2. 담도결찰(膽道結紮)로 인한 혈청(血淸) AST의 상승은 목향조기산(木香調氣散)과 해울조위탕(解鬱調胃湯)을 투여한 두 실험군(實驗群) 모두에서 억제되는 양상을 보였으며, 목향조기산(木香調氣散)을 투여한 실험군(實驗群)에서 억제되는 보다 나았으나 그 차이는 크지 않았다. 3. 담도결찰(膽道結紮)로 인한 血淸 ALT의 상승은 목향조기산(木香調氣散)과 해울조위탕(解鬱調胃湯)을 투여한 두 실험군(實驗群) 모두에서 억제되는 양상을 보였으며, 목향조기산(木香調氣散)의 억제효과가 해울조위탕(解鬱調胃湯)보다는 유의성이 인정되었다.

• 대한한의학방제학회지
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• 제6권1호
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• pp.119-139
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• 1998

간경변(肝硬變)은 각종(各種) 만성미만성간염(慢性彌滿性肝炎)이나 광범위(廣範圍)한 간장실질(肝臟實質)의 손상(損傷)이 계속적(繼續的)으로 발전(發展)하여 이루어진 결과(結果)이다. 주(主)된 병리적(病理的) 특징(特徵)은 간세포(肝細胞)의 변성(變成), 괴사(壞死) 후(後)에 나타나는 섬유조직(纖維組織)의 증식(增殖), 간세포(肝細胞)의 결절상(結節狀) 재생(再生), 가소엽(假小葉)의 형성(形成) 등(等)으로서, 이들 세가지의 변화(變化)가 뒤섞여 진행(進行) 되는 가운데, 간내(肝內) 혈관망(血管網)이 감소(減少)하거나 혈관망(血管網)에 이상(異狀) 함몰(陷沒)이 발생(發生)하는 것이다. 주(主)된 임상표현(臨床表現)은 간기능감퇴(肝機能減退)와 문맥압(門脈壓) 상승(上升)으로 인(因)한 비종대(脾腫大), 복수(腹水), 복벽정맥(腹壁靜脈)의 노장(怒張), 식도(食道)와 위저정맥(胃底靜脈)의 노장파열(怒張破裂), 간성혼수(肝性昏睡) 등(等)이 나타난다. 한의학(韓醫學)의 범주(範疇)로는 '적취(積聚), 징가, 황달(黃疸), 고창(鼓脹), 협통(脇痛), 단복창(單腹脹), 비괴' 등(等)에 해당(該當)되는 것으로 습열(濕熱)이 구울(久鬱)함에 따라 간(肝), 비(脾)가 손상(損傷)되고 이것이 더욱 오래되어 기체혈어(氣滯血瘀)로 발전(發展)하게 되는 병리변화(病理變化)를 갖는다. 이에 담도결찰(膽道結紮) 및 dimethylnitrosamine의 복강투여(腹腔投與)로 간경화(肝硬化)를 유발(誘發)하고, 울증(鬱證)에 다용하는 익국환과 익국보화환이 이러한 병증(病症)에 간기능보호작용(肝機能保護作用)이 있는가를 관찰(觀察)하고, 한의학적(韓醫學的) 병증(病症)의 분류(分類)에 따라 간질환(肝疾患)에 대(對)한 치료(治療)의 가능성(可能性)을 알아보고자 본(本) 실험(實驗)을 실시(實施)한 결과(結果), 유의성(有意性) 있는 결과(結果)를 얻었기에 보고(報告)하는 바이다.

• BMB Reports
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• 제53권6호
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• pp.311-316
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• 2020

Cholestasis is a condition in which the bile duct becomes narrowed or clogged by a variety of factors and bile acid is not released smoothly. Bile acid-induced liver injury is facilitated by necrotic cell death, neutrophil infiltration, and inflammation. Metformin, the first-line treatment for type 2 diabetes, is known to reduce not only blood glucose but also inflammatory responses. In this study, we investigated the effects of metformin on liver injury caused by cholestasis with bile acid-induced hepatocyte injury. Static bile acid-induced liver injury is thought to be related to endoplasmic reticulum (ER) stress, inflammatory response, and chemokine expression. Metformin treatment reduced liver injury caused by bile acid, and it suppressed ER stress, inflammation, chemokine expression, and neutrophil infiltration. Similar results were obtained in mouse primary hepatocytes exposed to bile acid. Hepatocytes treated with tauroursodeoxycholic acid, an ER stress inhibitor, showed inhibition of ER stress, as well as reduced levels of inflammation and cell death. These results suggest that metformin may protect against liver injury by suppressing ER stress and inflammation and reducing chemokine expression.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.108-114
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• 2002

• Toxicological Research
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• 제17권3호
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• pp.187-194
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• 2001

The oxidative stress causes the cell damage and death and thereby, stimulates membrane lipid peroxidation. In this study, the correlation between the lipid peroxidation product and the parameter of liver fibrosis (cirrhosis) was investigated in cholestasis induced rats. The Sprague-Dawley rats were divided into 3 groups (sham: sham operation, BDL/S-I and BDL/S-II : bile duct ligation/scission) and were observed for 2 or 4 weeks. After observation period, the organs were weighed and the ratio of organ weight/body weight was calculated. Sera and liver tissue were used for the measurement of malondealdehyde (MDA), parameter of clinical biochemistry, total collagen content and the staining. The ratio of organ weight/body weight in BDL/S-I and BDL/S-II was significantly increased compared to sham operated group. Serological parameters (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and Total bilirubin) in BDL/S-I and BDL/S-II group were significantly higher than those in sham operated group. Concentration of MDA in BDL/S-I (261%) and BDL/S-II(790%) was significantly increased compared to MDA in sham operated group. And the content of hydroxyproline (hyp) in BDL/S-I and BDL/S-II group was significantly increased 2~4 times than in sham operated group. The good correlations between hyp in liver tissue and MDA in sera of sham operated group and all operated group were found (r=0.825). The significantly higher value of MDA, hyp and serological parameters in BDL/S-I and BDL/S-II group suggests the stimulation of lipid peroxidation and chronic liver damage. Especially the activation of lipid peroxidation and the stimulation of liver fibrosis was stronger in BDL/S-II group than in BDL/S-I group. The stronger fibrosis, portal-portal septum formation, the more massive bile duct proliferation in portal triads and stroma, and hepatocytes swelling were observed in liver tissue of and BDL/S-II group compared to BDL/S-I group. Conclusively, a good correlation between MDA as a lipid peroxidation marker and hyp as a liver fibrotic parameter could be connected with the process of liver fibrosis. Moreover, cholestasis condition may cause jaundice, activation of lipid peroxidation, and collagen accumulation in liver. Additionally, optimal observation period of bile duct obstruction for the screening of antioxidant and antifibrotic effect in rats would be four weeks.

• Toxicological Research
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• 제34권3호
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• pp.241-247
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• 2018

Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes ($Col1{\alpha}1$, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.

• Toxicological Research
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• 제12권2호
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• pp.213-221
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• 1996

In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.

• BMB Reports
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• 제29권2호
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• pp.142-145
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• 1996

To investigate the cause of increased plasma catecholamine levels in liver disease, catechol-O-methyltransferase (COMT), which provides a major route of catabolism for circulating catecholamines, was studied under the cholestasis induced by mechanical biliary obstruction in rats. Monoamine oxidase (MAO) activity and the $K_m$ and $V_{max}$ values for both enzymes were also measured. Cytosolic, microsomal, and mitochondrial COMT activities in the cholestatic liver were significantly decreased throughout the experiment. Microsomal, and mitochondrial MAO activity in the cholestatic liver were also significantly decreased. Vmax values of COMT and MAO were lower. Serum COMT and MAO activities were detected after CBD ligation. These results indicate that plasma catecholamine levels are increased in liver disease due to decreased hepatic degradation of catecholamines by decreased activities of COMT and MAO. The decreased activity of these enzymes is caused by decreased biosynthesis and by flowage into the blood from the damaged hepatocyte.