• The Journal of Internal Korean Medicine
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• v.24 no.1
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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.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.129-136
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species (ROS) and free radical reactions. In this study, we investigated whether dried extracts of oriental medicine (LH) have antioxidant and antifibrotic effect under the biliary liver fibrosis (cirrhosis) c ondition. The female Sprague-Dawley rats were divided in six groups (Normal, N-LH, op-2, op-4, opLH-2, opLH-4) and were observed in 2 weeks or 4 weeks. For this purpose the rats were operated by bile duct ligation/scission (BDL/S), which induced to liver fibrosis and cirrhosis. After surgery, the prepared LH was administered p.o. 2 mι/day/rat in 2 weeks or 4 weeks for opLH groups. During the observation period, jaundices appeared in eyes, ears and tail of all BDL/S operated rats. And at the time of sacrifice, cholestasis was observed in proximal bile duct, especially the color of bile juice and urine in opLH-4 group showed more clear than op-2, op-4 and opLH-2 group. The value of clinical parameters and product of lipid peroxidation (MDA) in sera and the hydroxyproline (hyp) content in liver tissue were significantly increased in all liver fibrosis (cirrhosis) developed rats (p＜0.001~0.05). Among the clinical parameters of sera, value of BUN, ALP in opLH-4 group showed significantly lower than in op-4 group (p＜0.05, p＜0.001). The content of hyp in opLH-2, opLH-4 group (478.0 $\pm$ 134.3 $\mu\textrm{g}$/g 897.5 $\pm$ 118.2 $\mu\textrm{g}$/g) showed lower than in op-2, op-4 group (528.9 $\pm$ 220.7 $\mu\textrm{g}$/g, 1023.8 $\pm$ 277.1 $\mu\textrm{g}$/g) and then the value of MDA in opLH-4 was also significantly reduced to 59.4% of that in op-4 group (p＜0.001). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in op-2 group and in opLH-2 group, but the weak fibrosis and bile duct proliferation were observed in opLH-4 group compared with in op-4 group. Our data indicate that the 4 weeks treatment with LH extract suppressed lipid peroxidation and inhibited fibrotic (cirrhosis) process, and experimental cholestatic liver disease is associated with increased lipid peroxidation in BDL/S operated rats. Hence we concluded that the measurement of MDA and hyp can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis), and LH has been shown to have hepatoprotective effect, antifibrotic effect and antioxidant effect.

• Journal of the Korea Convergence Society
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• v.10 no.6
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• pp.65-71
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• 2019

The propose of this study has been conducted to examine expression of c-Myc and Thymosin-${\beta}4$ in liver cirrhosis model from liver fibrosis and For the method of study, the experiment was conducted in 2 groups; liver cirrhosis model experiment group due to liver fibrosis and control group with distilled water. This study outcome showed that liver cirrhosis model experiment group had significantly higher expression of c-Myc and Thymosin-${\beta}4$. with changes to hepatic tissue of special staining and electron microscopy. In conclusion, in clinical tests regarding liver function, molecular evaluation of c-Myc and Thymosin-${\beta}4$ and their expression along with serological change and histological assessment can be utilized as a reference for diagnosing liver disease for prevention and diagnosis of the disease, Based on this research in the future, we will carry out an in-depth study by adding the types of experimental groups and related genes.

• Journal of Microbiology and Biotechnology
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• v.32 no.3
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.39-56
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• 2002

Objective : The aim of this study is to investigate the inhibitory effect of lnjinchunggantang-derivative on acute and sub-acute hepatic fibrosis induced by $CCl_4$, and to compare the efficiency of lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma on acute and sub-acute hepatic fibrosis induced by $CCl_4$. Method : Western blotting for collagen type N, quantitative RT-PCR and gross & histological findings on liver tissue (Hematoxylin & Eosin stain, Reticulin stain, Masson-Trichrome stain) were studied. Results : In the study on collagen type N expression, lnjinchunggantangcderivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect in western blotting. In quantitative RT-PCR assay, lnjinchunggantang-derivative showed inhibitory effect on collagen type N expression in acute hepatic fibrosis model, whereas lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect on collagen type N expression in sub-acute hepatic fibrosis model. In the gross findings of acute and sub-acute hepatic fibrosis models,lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber. Zeloariae Rhizoma showed inhibitory effect on hepatic fibrosis in the order. In the histological findings of acute and sub-acute hepatic fibrosis models in Hematoxylin & Eosin, Reticulin and Masson-Trichrome staining, the liver of $CCl_4$-only group showed atrophy and necrotic change with white nodules whereas that of $CCl_4$+ Injinchunggantang-derivative showed no significant histological change with well preservation of the tone of the tissue, and Scirpi Tuber. Zeloariae Rhizoma and Salviae Radix group showed minimal fibrotic changes. In the scoring system of the extent of the inhibition of the hepatic fibrosis, lnjinchunggantang-derivative group showed statistically significant inhibitory effect(p<0.05) whereas Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed no statistically significant effect in the acute hepatic fibrosis model. In the sub-acute hepatic fibrosis model, lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed statistically significant effect (p<0.01). Conclusion : These results show that lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma have inhibitory effect in the order on hepatic fibrosis induced by $CCl_4$ by suppressing the expression of collagen type N, ultimately preventing liver cirrhosis. To obtain more credible results in this experiment, developement of a new experimental model more similar to human hepatic fibrosis is still needed.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.224-238
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• 1992

Hepatic fibrosis was induced in Sprague-Dawley rats to evaluate the ultrastructural changes of fat-storing cells(Ito cells). For experimental induction of liver fibrosis, the rats were administered intraperitoneally with 0.5ml of 50% $Ccl_4$ solution per Kg body weight, twice weekly for 12 weeks. The rats were sacrified every week. The liver tissues were examined under light and eletron microscopes. And the immunohistochemical study of desmin was also performed. The results were summarized as follows : Light microscopic findings : The cellular infiltrations with inflammatory cells and Kupffer cells developed from 1 week after $Ccl_4$ injection, and were the most severe in 4 weeks. The strong immunoreactivity for desmin was also evident in 4 weeks. The centrilobular necrosis and fibrosis developed from 2 weeks after injection, and the necrosis persisted until 8 weeks. The progress of fibrosis was accompanied by decreases in cellular infiltration and reactivity for desmin, and increased gradual nodular formation was also observed. The cirrhosis was developed after 10 weeks. Electron microscopic findings : An increase in number of fat-storing cells was observed from 1 week after injection. Transitional cells characterized by a depletion of lipid droplets and a hypertrophy of the rER appeared after 2 weeks. The number of transitional cells with abundant collagen fibers in the extracellular spaces increased in 4 weeks. With progression of fibrosis the number of fat-storing cells decreased and proliferating fibroblasts with dilated rER were observed. According to these results it was revealed that there was an apparent transition from fat-storing cells to transitional cells and to fibroblasts. These cells had a few similar characteristics and may belong to the same cell population. Thus it was suggested that fat-storing cells might play an important role in hepatic fibrosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1525-1531
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• 2008

Acer tegmentosum Max which is one of the specialized wildness medicinal herbs in gangwon province, has been widely used for hepatitis, liver cirrhosis, hepatic cancer, leukemia, diabetes mellitus, renal necrosis and edema, etc. In this study, the antioxidative and hepatoprotective effects of in vitro and in vivo were investigated in order to evaluate the possibility as hepatoprotective agents. Oral administration of methanol and butanol extact of Acer tegmentosum Max to d-galactosamine (D-GaIN) induced experimental liver injured rats was significantly reduced activities of marker enzymes(AST, ALT) and LDH activity in serum. Salidroside(Sal) isolated from the BuOH extract of Acer termentosum Max potenty showed the scavenzing effect on DPPH and inhibitory effect on lipid peroxidation. And significantly decrcease of MDA level in liver and activities of SOD GSH-Px and catalase were significantly improved by the treatment of Sal. Results of this study revealed that Sal could afford a significant protection in the alleviation of D-GaIN-induced hepatocellular injury.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.22-38
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• 1998

This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1067-1072
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• 2006

Purpose : The purpose of this study was to examine the clinical courses and long-term outcomes of children with Allagille syndrome in Korea, and to evaluate the prognostic potentials of identified variables. Methods : We reviewed the clinical manifestations and outcomes of 30 children with Alagille syndrome, investigated from 1984 to 2006 until the end of this study (defined as death or last visit; mean follow-up : 5 years). Results : Cholestasis occurred in 100 percent, cardiovascular abnormalities in 83.3 percent, butterfly vertebrae in 30.0 percent, posterior embryotoxon in 43.3 percent, and a characteristic facial appearance in 100 percent. At study conclusion, of these 30 patients, eight had died (26.7 percent); six related to Alagille syndrome. Five patients died of a liver disease complication. Liver transplantation was carried out in five of the 30 patients (16.7 percent) and one of these died due to hyperacute rejection. At age two, cholestasis improved in 17 of the 30 patients. Those who had severe cholestasis at 2 years of age tended to have a complication, such as liver cirrhosis or liver transplantation, or to have died. Conclusion : Hepatic complications account for the most mortalities in patients with Alagille syndrome. Careful and complete assessments should be made in children who have cholestasis at 2 years of age. Further investigations of more cases are required.