• Archives of Pharmacal Research
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• v.28 no.1
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• pp.44-48
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• 2005

Phytochemical investigation of the MeOH extract of the root barks of Cudrania tricuspidata Bureau (Moraceae), as guided by hepatoprotective activity in vitro, furnished four isoprenylated xanthones, cudratricusxanthone A (1), cudraxanthone L (2), cudratricusxanthone E (3), and macluraxanthone B (4). All of these compounds showed the significant hepatoprotective effect on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. Compounds 1, 2, and 4 also exhibited the significant hepatoprotective effect on nitrofurantoin-induced cytotoxicity in human liver-derived Hep G2 cells.

• Natural Product Sciences
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• v.18 no.4
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• pp.221-226
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• 2012

Hesperidin (HES) is a bioflavonoid with antioxidant, anti-inflammatory and anti-diabetic properties. IL-6 is well known as a primary proinflammatory cytokine that contributes to impaired insulin signaling in liver. This study was to investigate whether HES improves IL-6-mediated impairment of insulin sensitivity in liver. Hepa-1c1c7 cells were pre-treated with 50 and $100{\mu}M$ HES in complete media for 1 h and then cultured in the presence or absence of IL-6 (20 ng/ml). These results demonstrated that HES restored IL-6-suppressed expression of IRS-1 protein, downregulated IL-6-increased expression of CRP and SOCS-3 mRNA, and inhibited LPS-induced production of IL-6 in Hepa-1c1c7 cells. These findings indicate that HES may ameliorate hepatic insulin resistance via improvement of IL-6-mediated impaired insulin signaling in hepatocytes.

• Natural Product Sciences
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• v.19 no.4
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• pp.360-365
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• 2013

Baicalin has antioxidant, anti-inflammatory and anti-diabetic properties. IL-6 is a primary proinflammatory cytokine that contributes to impaired insulin signaling in liver. This study was carried out to investigate whether baicalin improves IL-6-mediated insulin resistance in liver. Hepa-1c1c7 cells were pre-treated with 50 and 100 ${\mu}M$ baicalin in complete media for 1 h and then cultured in the presence or absence of IL-6 (20 ng/ml). These results demonstrated that baicalin restored IL-6-suppressed expression of insulin receptor substrate (IRS)-1 protein, downregulated IL-6-increased gene expression of C-reactive protein (CRP) and suppressor of cytokine signaling (SOCS)-3, and inhibited LPS-induced production of IL-6 in Hepa-1c1c7 cells. These findings indicate that baicalin may ameliorate hepatic insulin resistance via improvement of IL-6-mediated impaired insulin signaling in hepatocytes.

• Korean Journal of Veterinary Pathology
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• v.7 no.1
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• pp.67-69
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• 2003

Three mature layer chickens from a farm in which chickens showed green diarrhea, cyanosis, lethargy, loss of appetite were pathologically examined. Grossly, multiple variable sized caseous nodules were detected in the liver, intestinal serosa and mesentery. In addition, parathypoid nodules in the liver and fibrous serositis on the several peritoneal organs and tissues were noticed. One of spleens had multiple infarction areas. Histologically caseous nodules consisted of central caseous core and peripheral epithelioid cells overlying the fibrous connective tissue. Multinucleated giant cells were scattered between the epithelioid cells and fibrous connective tissue. In these nodules Gram negative cocobacilus bacterial colonies were present, whereas Periodic Schiff reaction and Ziehl-Neelsen stain detected neither fungi nor acid fast bacteria. From these results multiple granulomas might be induced by Escherichia coli. In addition, severe Ascafdiodf and Salmonellosis were coinfected in these chickens.

• Journal of Ginseng Research
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• v.16 no.3
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• pp.210-216
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• 1992

The effect of saponin extracted from Panax grneng CA Meyer on DNA repair and replicative DNA synthesis were examined in CHO-Kl cells cotreated with benzo(a)pyrene and rat liver S-15 fraction. The DNA strand breaks inititated by benzo(a)pyrene metabolites were measured by alkaline election technique. The addition of ginseng saponin to the culture media resulted in decrease of benzo(a)pyrene-induced DNA strand breaks, and restored the suppressed-semiconservative-DNA-synthesis by the carcinogen. DNA repair synthesis in the damaged cells was also elevated by the ginseng treatment when the repairing activites were measured for the (3H)-thymidine incorporation into the carcinogen damaged cellular DNk Comparative analysis of DNA-adduces of benzo(a)pyrene metabortes in microsomes suggested that ginseng saponin treatment in rats reduced the formation of electrophilic metabolites of benzo (a)-pyrene in the rat liver microsomes.

• Bulletin of the Korean Chemical Society
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• v.33 no.6
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• pp.1983-1988
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• 2012

Stem cell transplantation is emerging as a possible new treatment for liver cirrhosis, and recent animal studies have documented the benefits of stem cell therapy in a hepatic fibrosis model. However, the underlying mechanism of stem cell therapy is still unclear. Among the proposed mechanisms, the cell replacement mechanism is the oldest and most important, in which permanently damaged tissue can be replaced by normal tissue to restore function. In the present study, Cy5.5-labeled superparamagnetic iron oxide (SPIO) was used to label human mesenchymal stem cells. The uptake of fluorescently labeled nanoparticles enabled the detection and monitoring of the transplanted stem cells; therefore, we confirmed the direct incorporation and differentiation of SPIO into the hepatocyte-like transplanted stem cells by detecting human tyrosine aminotransferase (TAT), well-known enzymatic marker for hepatocyte-specific differentiation.

• Applied Microscopy
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• v.39 no.4
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• pp.355-363
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• 2009

The purpose of this study was to demonstrate the effect of Momordica Charantia L. water extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the rats liver and kidney caused by lead acetate. Rat approximately 250 g in weight were grouped into the control, lead acetate treated, and the Momordica Charantia L. boiling water extracts treated after lead acetate groups. Lead acetate (1,000 ppm) and Momordica Charantia L. water extracts (5%, 10%) were delivered drinking water. Serum AST, ALT and BUN were measured, histological alteration of liver and kidney were examined by light microscopy. Momordica Charantia L. extract group was decreased serum AST, ALT and BUN level induced by lead. Optical observations of liver tissue, lead group were observed necrosis of hepatic cells and infiltration of inflammatory cells, but Momordica Charantia L. extract group was observed only slight infiltration of inflammatory cells around the central vein. Optical observations of kidney tissue, lead acetate induced atrophy and necrosis of glomerulus and infiltration of inflammatory cell around renal tubule. For the group treated with Momordica charantia L. extract, the glomerulus was similar to the control, some around the renal tubule was observed infiltration of inflammatory cells. In conclusion, Momordica Charantia L. water extract may protect the lead-induced toxicity on liver and kidney.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.163-172
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• 2004

Mast cells (MCs) have been implicated in the pathogenesis of tissue fibrosis. However, the role of MC in the development of liver fibrosis has not been fully elucidated. Stem cell factor (SCF) is known to recruit MCs to the liver following injury as it induces mast cell proliferation, survival and differentiation from resident tissue precursors. This study examines the interaction between activated hepatic stellate cells (HSCs) and MCs in rat fibrotic liver, and SCF production by HSCs during culture in vitro. Rats were studied 4, 7, 14 and 21 days after bile duct ligation (BDL). Fibrogenesis was assessed by a measurement of collagen stained with sirius red F3B. Activated HSCs and MCs were identified by ${\alpha}$-smooth muscle actin (${\alpha}-SMA$) immunohistochemical and alcian blue staining and measured by a computerized image analysis system. SCF production was determined in rat HSC cultures using Western blotting. Mild fibrotic changes were noted in BDL rat livers as early as 4 days after induction of cholestasis. Significant expansion and organization of fibrous tissue has occurred in day 14 BDL rats which progressed to bridging fibrosis by day 21. In BDL rats, both a large number of activated HSCs and MCs were detected in portal tracts and fibrous septa. Both area of activated HSCs infiltration and density of MCs were significantly higher in all BDL group compared with Shams. In BDL rats, both areas of activated HSCs infiltration and density of MCs were no significant difference between day 4 and 7 and were significantly higher in day 14. However, the areas of activated HSCs infiltration were significantly lesser in day 21 and the densities of MCs were significantly higher in day 21 compared with day14 BDL. In BDL rats, both areas of activated HSCs infiltration and density of MCs were highly correlated with areas of fibrosis. Western blotting showed that SCF protein was consistently produced in activated HSCs by culture on plastic and freshly isolated HSCs expressed relatively little 30kD SCF compared to late primary culture activated HSCs (day 14) and passaged HSCs. These results suggest that HSCs activated in vitro produce SCF, and may play an important role in recruiting mast cells to the liver during injury and fibrosis.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.261-265
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• 2007

Hydroxyproline (HYP) is a post-translational product of proline hydroxylation catalyzed by an enzyme prolyl 4-hydroxylase (P4H) which plays a crucial role in the synthesis of all collagens. Considering the role of collagen and its significance in many clinically important diseases such as liver fibrosis, a great deal of attention has been directed toward the development of an assay at cell-based system. The reason is that cell-based assay system is more efficient than enzyme-based in vitro system and takes much less time than in vivo system. Several assay procedures developed for P4H are laborious, time-consuming and not feasible for the massive-screening. Here, we report the cell-based assay method of prolyl 4-hydroxylase in immortalized rat hepatic stellate HSC-T6 cells. To optimize the cell culture condition to assay for HYP content, various concentrations of reagents were treated for different times in HSC-T6 cells. Our data showed that the treatment with ascorbate in a hypoxic condition for 24 h resulted in the maximal increase of HYP by 1.8 fold. Alternatively, cobalt chloride ($5\;{\mu}M$) and ascorbate ($50\;{\mu}M$) in normoxic states exhibited similar effect on the production of HYP as in a hypoxic condition. Therefore, cobalt chloride can be substituted for a hypoxic condition when an anaerobic chamber is not available. Rosiglitazone and HOE077, known as inhibitors of collagen, synthesis decreased P4H enzyme activity by 32.3% and 15%, respectively, which coincided with previous reports from liver tissues. The level of the smooth muscle ${\alpha}$-actin, a marker of activated stellate cells, was significantly increased under hypoxia, suggesting that our experimental condition could work for screening the anti-fibrotic compounds. The assay procedure took only 3 days after treatment with agents, while assays from the primary stellate cells or liver tissues have taken several weeks. Considering the time and expenses, this assay method could be useful to screen the compounds for the inhibitor of prolyl 4-hydroxylase.

• Herbal Formula Science
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• v.13 no.2
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• pp.111-123
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• 2005

The purpose of this study was to investigate the anticancer effects of Caesalpiniae Lignum (Somok) on HepG2 cells, a human liver cancer cell line. To study the cytotoxic effect of Caesalpiniae Lignum methanol extract (CL-MeOH) on HepG2 cells, the cells were treated with various concentrations of CL-MeOH and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. CL-MeOH reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of CL-MeOH. The activation of caspase 3 and the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, was examined by western blot analysis. CL-MeOH decreased procaspase 3 level in a dose-dependent manner and induced the clevage of PARP at concentration> $200{\mu}/ml$. Mitogen-activated protein (MAP) kinase signaling cascades are multi-functional signaling networks that influence cell growth, differentiation, apoptosis, and cellular responses to stress. CL-MeOH-induced MAPK activation was examined by Western blot for phosphorylated ERK, p38 and JNK. CL-MeOH significantly increased p38 phosphorylation and JNK phosphorylation in a dose-dependent manner. Inhibition of p38 function using the selective inhibitor SB20358O results in inhibition of apoptosis by CL-MeOH. These results suggest that CL-MeOH-induced apoptosis is MAP kinase-dependent apoptoric pathway. These results suggest that CL-MeOH is potentially useful as a chemotherapeutic agent in human liver cancer.