• Advances in Traditional Medicine
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• 제2권2호
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• pp.94-100
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• 2002

Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic diseases. In this study, the antifibrotic effects of GLM001 on liver cirrhosis were examined in bile duct ligated rats and patients with hepatic diseases. GLM001 (250 mg/kg rat weight/ day) was administrated to cirrhotic rats for 4 weeks and to humans for 14 weeks. Bile duct ligated rats significantly increased liver collagen content and biochemical markers of hepatic injury. Liver histology showed collagen fiber deposition was increased and the normal architecture was lost with large zones of necrosis being observed frequently. GLM001 administrated rats showed significantly decreased liver collagen content, and accumulation of collagen fiber in histological analysis. Patients, who were treated with GLM001, showed decreases in biochemical markers of hepatic diseases. These results demonstrate the usefulness of GLM001 as an antifibrotic agent for liver cirrhosis.

• 대한임상검사과학회지
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• 제43권4호
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• pp.194-204
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• 2011

This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.327-332
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• 2001

The antifibrotic effects of hot water extract (WEC), intracellular biopolymer (IPC) and extracellular biopolymers (EPC) from mycelial liquid culture of Cordyceps militaris on liver fibrosis were studied. Liver fibrosis was induced by a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats. In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline content in liver were dramatically increased. The WEC or IPC treatment (30mg/kg/day for 4 weeks, p.o.) in BDL/S rats reduced the serum AST, ALT and ALP levels significantly (p<0.01). The EPC treatment (30 mg/kg /day for 4 weeks, p.o.) reduced the serum ALT, AST and ALP levels significantly (p<0.01). Malondialdehyde contents in liver treated with WEC, IPC or EPC were significantly reduced (p <0.05). But Liver hydroxyproline content was decreased only in EPC treated BDL/S rats to 55% that of BDL/S control rats (p < 0.01). The morphological characteristics and expression of alpha smooth muscle like actin in fibrotic liver, which appeared in BDL/S control group were improved in EPC treated fibrotic liver. These results indicate that IPC (30 mg/kg /day for 4 weeks, p.o.) has an antifibrotic effect on fibrotic rats induced by BDL/S.

• Archives of Pharmacal Research
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• 제23권6호
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• pp.613-619
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• 2000

We investigated the expression profiles of rat fibrotic liver induced by bile duct ligation and scission (BDL/S) using the 3'-directed cDNA libraries. The possibility that the 3'-directed cDNA library represents the mRNA population faithfully was examined by northern blots. During the northern analysis based on fibrotic liver expression profile, we found for the first time that purine specific sodium nucleoside cotransporter (SPNT) was upregulated in BDL/S-induced fibrotic liver. To determine whether the accumulation of bile juice could affect the expression of SPNT mRNA or not, we examined the change of SPNT mRNA expression at 3, 14, 28 days after BDL/S operation. No change in SPNT expression was observed in rat liver at 3 days after surgery. In contrast, there were significant increases in SPNT expression at 14 and 28 days after surgery. We also examined whether chronic liver damage affected SPNT mRNA expression. SPNT mRNA level was significantly increased in BDL/S-induced fibrotic rat liver, whereas no significant change was obserbed in fibrotic livers chronically exposed to carbon tetrachloride or dimethylnitrosamine. From the above results, although further study might be needed, it was considered that the increment of SPNT mRNA in BDL/S liver morphological compatibility to human was remarkable.

• 대한의생명과학회지
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• 제19권2호
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• pp.158-163
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• 2013

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

• Natural Product Sciences
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• 제15권2호
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• pp.101-105
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• 2009

We previously reported that a novel cerebroside, LCC, isolated from the fruits of Lycium chinense (Solanaceae), significantly exerted hepatoprotective activity against both the carbon tetrachloride-induced and galactosamine-induced toxicities in primary cultures of rat hepatocytes. In the present study, we further attempted to determine the effect of LCC on hepatic fibrosis in animal model. Hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 5 weeks. Treatment of BDL rats with LCC significantly reduced collagen deposition and the activities of serum alkaline phosphatase and ${\gamma}$-glutamyl transpeptidase. In addition, the LCC treatment of BDL rats significantly preserved the decreased hepatic glutathione as well as the activities of glutathione reductase and catalase in BDL rats. From the results, it can be speculated that LCC might exert antifibrotic activity in rats with BDL, in part, through the preservation of antioxidant enzymes and hepatic glutathione.

• 대한의생명과학회지
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• 제10권2호
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• pp.93-98
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• 2004

The effects of intravenously administered of high concentration of taurocholic acid (TCA) on $\alpha$-D- and $\beta$-D-mannosidase activities in rat liver lysosomes were studied. These liver lysosomal enzymes, and serum lysosomal $\alpha$-D- and $\beta$-D-mannosidase isozymes activities were determined in experimental rats with common bile duct ligation (CBDL). The liver lysosomal $\beta$-D-mannosidase activity as well as the serum lysosomal $\alpha$-D- and $\beta$-D-mannosidase isozymes activities were found to be significantly increased in the CBDL plus TCA injected group than in the control group such as CBDL alone group. However, the liver lysosomal $\alpha$-D-mannosidase activity was found to be significantly decreased in the CBDL plus TCA injected group. The above results suggest that TCA repress the biosynthesis of the lysosomal $\alpha$-D-mannosidase and induce the biosynthesis of the lysosomal $\beta$-D-mannosidase in the liver. And that the elevated serum lysosomal $\alpha$-D- and $\beta$-D-mannosidase isozymes activities are most likely due to increased hepatocyte membrane permeability caused by TCA mediated liver cell necrosis.

• 대한한의학방제학회지
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• 제12권2호
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• pp.109-117
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• 2004

This study was carried out to investigate the liver protective effects of extracts from Persicae Semen (WT-003, WT-005, WT-006). The acute hepatic injury was induced by intraperitoneal injection of alpha-naphtylisothiocyanate (75 mg/kg, p.o.) and treated with WT-006 (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day). The experimental hepatic fibrosis was induced by bile duct ligation／scission(BDL/S), duration of 4 weeks and treated with WT-003, WT-005 or WT-006 (200 mg/kg/days for 4 week). In acute liver injury, WT-006 (200 or 400 mg/kg) lowered serum alanine transferase(ALT) and aspartate transferase(AST) significantly. In fibrotic rats, WT-006 treatment inhibited the hydroxyproline deposition in liver and lowered serum AST, ALT and ALP, significantly. These results suggest WT-006 extract, which does not contain amygdalin, from Persicae Semen have liver protective and antifibrotic effects in rats.

• 약학회지
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• 제41권5호
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• pp.622-628
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• 1997

Hepatic cirrhosis is a common response to chronic liver injury from many causes and is one of the most common cause of all deaths. This study was carried out to compare experimental hepatic cirrhosis in rats to understand this disease and to apply for the pharmacokinetics in disease state. Following three kinds of experimental models were induced; 1) Bile duct ligation/scission (BDL/S), 2) N, N-dimethylnitrosamine(DMN), 3) Carbon tetrachloride. The hepatic cirrhosis was characterized by examing the liver/body weight ratio, serum biochemical values, hydroxyproline content in liver and histopathological lesions in cirrhotic rat liver. The results are as follows : (1) In BDL/S, the liver was enlarged to 250% of normal liver. In contrast the liver was shrinked to 48% and 78% of the normal liver in DMN and carbon tetrachloride, respectively. (2) In carbon tetrachloride and BDL/S, the serum ALT, AST, ALP and total bilirubin levels were significantly increased to 200~300% of normal level, while ALT and total bilirubin levels were significantly increased in DMN group. (3) Hydroxyproline content in cirrhotic rat liver was significantly 200~500% higher than that of normal liver. (4) Nodular formation with fibrosis was observed in BDL/S, DMN, carbon tetrachloride induced cirrhotic rat liver.

• 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.