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http://dx.doi.org/10.5142/jgr.2013.37.45

Red ginseng extract protects against carbon tetrachloride-induced liver fibrosis  

Ki, Sung Hwan (College of Pharmacy, Chosun University)
Yang, Ji Hye (College of Pharmacy, Chosun University)
Ku, Sae Kwang (Medical Research Center for Global Herbal Formulation, College of Korean Medicine, Daegu Haany University)
Kim, Sang Chan (Medical Research Center for Global Herbal Formulation, College of Korean Medicine, Daegu Haany University)
Kim, Young Woo (Medical Research Center for Global Herbal Formulation, College of Korean Medicine, Daegu Haany University)
Cho, Il Je (Medical Research Center for Global Herbal Formulation, College of Korean Medicine, Daegu Haany University)
Publication Information
Journal of Ginseng Research / v.37, no.1, 2013 , pp. 45-53 More about this Journal
Abstract
Korean red ginseng, the processed root of Panax ginseng Meyer, has been frequently used for various therapeutic purposes in oriental medicine. The present study investigated the possible effect of Korean red ginseng extract (RGE) for the treatment of liver fibrosis in mice injected with carbon tetrachloride ($CCl_4$) for 4 wk. Liver injuries were assessed by blood biochemistry and histopathology in mice treated with $CCl_4$ alone or $CCl_4$+ RGE (30, 100, and 300 mg/kg). Concomitant treatment with RGE and $CCl_4$ (three times/wk for 4 wk) effectively inhibited liver fibrosis as evidenced by decreases in plasma alanine and aspartate aminotransferases, as well as by the percentages of degenerative regions, numbers of degenerative hepatocytes, and collagen accumulation in hepatic parenchyma. Treatment with $CCl_4$ for 4 wk increased mRNA levels of transforming growth factor ${\beta}1$ and plasminogen activator inhibitor 1 in fibrogenic liver, whereas RGE (30, 100, and 300 mg/kg) significantly blocked the induction of fibrogenic genes by $CCl_4$. Similarly, RGE also prevented transforming growth factor ${\beta}1$-mediated induction of fibrogenic genes in human hepatic stellate cell lines. More importantly, RGE markedly reduced the number of ${\alpha}$-smooth muscle actin-positive cells in liver tissue. This study implies that RGE efficaciously protects against the liver fibrosis induced by chronic $CCl_4$ treatment, and may therefore have potential to treat liver disease.
Keywords
Panax ginseng; Korean red ginseng; Liver fibrosis; Transforming growth factor ${\beta}1$; ${\alpha}$-smooth muscle actin;
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1 Lo YT, Tsai YH, Wu SJ, Chen JR, Chao JC. Ginsenoside Rb1 inhibits cell activation and liver fibrosis in rat hepatic stellate cells. J Med Food 2011;14:1135-1143.   DOI   ScienceOn
2 Geng J, Peng W, Huang Y, Fan H, Li S. Ginsenoside-Rg1 from Panax notoginseng prevents hepatic fibrosis induced by thioacetamide in rats. Eur J Pharmacol 2010;634:162-169.   DOI   ScienceOn
3 Cho IJ, Kim YW, Han CY, Kim EH, Anderson RA, Lee YS, Lee CH, Hwang SJ, Kim SG. E-cadherin antagonizes transforming growth factor $\beta 1$ gene induction in hepatic stellate cells by inhibiting RhoA-dependent Smad3 phosphorylation. Hepatology 2010;52:2053-2064.   DOI   ScienceOn
4 Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998;153:515-525.   DOI   ScienceOn
5 Pierce RA, Glaug MR, Greco RS, Mackenzie JW, Boyd CD, Deak SB. Increased procollagen mRNA levels in carbon tetrachloride-induced liver fibrosis in rats. J Biol Chem 1987;262:1652-1658.
6 Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med 2006;10:76-99.   DOI   ScienceOn
7 Seo EY, Kim WK: Red ginseng extract reduced metastasis of colon cancer cells in vitro and in vivo. J Ginseng Res 2011; 35:315-324.   DOI   ScienceOn
8 Kim HY, Kang KS, Yamabe N, Yokozawa T. Comparison of the effects of Korean ginseng and heat-processed Korean ginseng on diabetic oxidative stress. Am J Chin Med 2008;36:989-1004.   DOI   ScienceOn
9 Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng: basic and clinical trials. Clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci 2004;95:158-162.   DOI   ScienceOn
10 Heo JH, Lee ST, Oh MJ, Park HJ, Shim JY, Chu K, Kim MH: Improvement of cognitive deficit in Alzheimer's disease patients by long term treatment with Korean red ginseng. J Ginseng Res 2011; 35:457-461.   DOI   ScienceOn
11 Wu YL, Wan Y, Jin XJ, OuYang BQ, Bai T, Zhao YQ, Nan JX. 25-OCH3-PPD induces the apoptosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-$\kappa B$ activation. Chem Biol Interact 2011;194:106-112.   DOI   ScienceOn
12 Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209-218.   DOI   ScienceOn
13 Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008;134:1655-1669.   DOI   ScienceOn
14 Lee S, Lee MS, Kim CT, Kim IH, Kim Y. Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 2012;13:5729-5739.   DOI
15 Kim AD, Kang KA, Zhang R, Lim CM, Kim HS, Kim DH, Jeon YJ, Lee CH, Park J, Chang WY et al. Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase. Environ Toxicol Pharmacol 2010;30:134-140.   DOI   ScienceOn
16 El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-2576.   DOI   ScienceOn
17 Lim JY, Oh MA, Kim WH, Sohn HY, Park SI. AMP-activated protein kinase inhibits TGF-β-induced fibrogenic responses of hepatic stellate cells by targeting transcriptional coactivator p300. J Cell Physiol 2012;227:1081-1089.   DOI   ScienceOn
18 Caligiuri A, Bertolani C, Guerra CT, Aleffi S, Galastri S, Trappoliere M, Vizzutti F, Gelmini S, Laffi G, Pinzani M et al. Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells. Hepatology 2008;47:668-676.
19 Cho IJ, Kim SH, Kim SG. Inhibition of TGFbeta1-mediated PAI-1 induction by oltipraz through selective interruption of Smad 3 activation. Cytokine 2006;35:284-294.   DOI   ScienceOn
20 Simonetti RG, Camma C, Fiorello F, Politi F, D’Amico G, Pagliaro L. Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig Dis Sci 1991;36:962-972.   DOI
21 Tamayo RP. Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? Hepatology 1983;3:112-120.
22 Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007;25:185-209.   DOI   ScienceOn
23 Kruse JJ, Bart CI, Leer JW, Wondergem J. Detection and quantitative measurement of transforming growth factor-beta1 (TGF-beta1) gene expression using a semi-nested competitive PCR assay. Cytokine 1999;11:179-185.   DOI   ScienceOn
24 Seki T, Imai H, Uno S, Ariga T, Gelehrter TD. Production of tissue-type plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in mildly cirrhotic rat liver. Thromb Haemost 1996;75:801-807.
25 Dennler S, Itoh S, Vivien D, ten Dijke P, Huet S, Gauthier JM. Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. EMBO J 1998;17:3091-3100.   DOI   ScienceOn
26 Hagiwara H, Kaizu K, Uriu K, Noguchi T, Takagi I, Qie YL, Seki T, Ariga T. Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic rat models. Thromb Res 2003;111:301-309.   DOI   ScienceOn
27 Kang KW, Kim YG, Cho MK, Bae SK, Kim CW, Lee MG, Kim SG. Oltipraz regenerates cirrhotic liver through CCAAT/enhancer binding protein-mediated stellate cell inactivation. FASEB J 2002;16:1988-1990.   DOI
28 Fujii T, Fuchs BC, Yamada S, Lauwers GY, Kulu Y, Goodwin JM, Lanuti M, Tanabe KK. Mouse model of carbon tetrachloride induced liver fibrosis: histopathological changes and expression of CD133 and epidermal growth factor. BMC Gastroenterol 2010;10:79.   DOI   ScienceOn
29 Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol 2007;170:1807-1816.   DOI   ScienceOn
30 Lee HJ, Lee YH, Park SK, Kang ES, Kim HJ, Lee YC, Choi CS, Park SE, Ahn CW, Cha BS et al. Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats. Metabolism 2009;58:1170-1177.   DOI   ScienceOn
31 Rej R. Aspartate aminotransferase activity and isoenzyme proportions in human liver tissues. Clin Chem 1978; 24:1971-1979.