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Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2015 | Research article

Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease

Authors: Jae-Chul Jung, Yun-Hee Lee, Sou Hyun Kim, Keuk-Jun Kim, Kyung-Mi Kim, Seikwan Oh, Young-Suk Jung

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

Background

Our previous study suggested that licorice has anti-inflammatory activity in lipopolysaccharide-stimulated microglial cells and anti-oxidative activity in tert-butyl hydroperoxide–induced oxidative liver damage. In this study, we evaluated the effect of licorice on chronic alcohol-induced fatty liver injury mediated by inflammation and oxidative stress.

Methods

Raw licorice was extracted, and quantitative and qualitative analysis of its components was performed by using LC–MS/MS. Mice were fed a liquid alcohol diet with or without licorice for 4 weeks.

Results

We have standardized 70 % fermented ethanol extracted licorice and confirmed by LC-MS/MS as glycyrrhizic acid (GA), 15.77 ± 0.34 μg/mg; liquiritin (LQ), 14.55 ± 0.42 μg/mg; and liquiritigenin (LG), 1.34 ± 0.02 μg/mg, respectively. Alcohol consumption increased serum alanine aminotransferase and aspartate aminotransferase activities and the levels of triglycerides and tumor necrosis factor (TNF)-α. Lipid accumulation in the liver was also markedly induced, whereas the glutathione level was reduced. All these alcohol-induced changes were effectively inhibited by licorice treatment. In particular, the hepatic glutathione level was restored and alcohol-induced TNF-α production was significantly inhibited by licorice.

Conclusion

Taken together, our data suggests that protective effect of licorice against alcohol-induced liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.
Appendix
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Literature
1.
go back to reference Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;150(3):781–90.CrossRefPubMed Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;150(3):781–90.CrossRefPubMed
2.
go back to reference Cantelli-Forti G, Maffei F, Hrelia P, Bugamelli F, Bernardi M, D’Intino P, et al. Interaction of licorice on glycyrrhizin pharmacokinetics. Environ Health Perspect. 1994;102 Suppl 9:65–8.PubMedCentralCrossRefPubMed Cantelli-Forti G, Maffei F, Hrelia P, Bugamelli F, Bernardi M, D’Intino P, et al. Interaction of licorice on glycyrrhizin pharmacokinetics. Environ Health Perspect. 1994;102 Suppl 9:65–8.PubMedCentralCrossRefPubMed
3.
go back to reference Li HY, Xu W, Su J, Zhang X, Hu LW, Zhang WD. In vitro and in vivo inhibitory effects of glycyrrhetinic acid on cytochrome P450 3A activity. Pharmacology. 2010;86(5-6):287–92.CrossRefPubMed Li HY, Xu W, Su J, Zhang X, Hu LW, Zhang WD. In vitro and in vivo inhibitory effects of glycyrrhetinic acid on cytochrome P450 3A activity. Pharmacology. 2010;86(5-6):287–92.CrossRefPubMed
4.
go back to reference Liao WC, Lin YH, Chang TM, Huang WY. Identification of two licorice species, Glycyrrhiza uralensis and Glycyrrhiza glabra, based on separation and identification of their bioactive components. Food Chem. 2012;132(4):2188–93.CrossRef Liao WC, Lin YH, Chang TM, Huang WY. Identification of two licorice species, Glycyrrhiza uralensis and Glycyrrhiza glabra, based on separation and identification of their bioactive components. Food Chem. 2012;132(4):2188–93.CrossRef
5.
go back to reference Montoro P, Maldini M, Russo M, Postorino S, Piacente S, Pizza C. Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI/MS/MS and determination of major metabolites by LC-ESI/MS and LC-ESI/MS/MS. J Pharm Biomed Anal. 2011;54(3):535–44.CrossRefPubMed Montoro P, Maldini M, Russo M, Postorino S, Piacente S, Pizza C. Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI/MS/MS and determination of major metabolites by LC-ESI/MS and LC-ESI/MS/MS. J Pharm Biomed Anal. 2011;54(3):535–44.CrossRefPubMed
6.
go back to reference Farag MA, Porzel A, Wessjohann LA. Comparative metabolite profiling and fingerprinting of medicinal licorice roots using a multiplex approach of GC-MS, LC-MS and 1D NMR techniques. Phytochemistry. 2012;76:60–72.CrossRefPubMed Farag MA, Porzel A, Wessjohann LA. Comparative metabolite profiling and fingerprinting of medicinal licorice roots using a multiplex approach of GC-MS, LC-MS and 1D NMR techniques. Phytochemistry. 2012;76:60–72.CrossRefPubMed
7.
go back to reference Fu Y, Chen J, Li YJ, Zheng YF, Li P. Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice. Food Chem. 2013;141(2):1063–71.CrossRefPubMed Fu Y, Chen J, Li YJ, Zheng YF, Li P. Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice. Food Chem. 2013;141(2):1063–71.CrossRefPubMed
8.
go back to reference Gafner S, Bergeron C, Villinski JR, Godejohann M, Kessler P, Cardellina JH, et al. Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification. J Nat Prod. 2011;74(12):2514–9.CrossRefPubMed Gafner S, Bergeron C, Villinski JR, Godejohann M, Kessler P, Cardellina JH, et al. Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification. J Nat Prod. 2011;74(12):2514–9.CrossRefPubMed
9.
go back to reference Chung WT, Lee SH, Kim JD, Sung NS, Hwang B, Lee SY, et al. Effect of the extracts from Glycyrrhiza uralensis Fisch on the growth characteristics of human cell lines: Anti-tumor and immune activation activities. Cytotechnology. 2001;37(1):55–64.PubMedCentralCrossRefPubMed Chung WT, Lee SH, Kim JD, Sung NS, Hwang B, Lee SY, et al. Effect of the extracts from Glycyrrhiza uralensis Fisch on the growth characteristics of human cell lines: Anti-tumor and immune activation activities. Cytotechnology. 2001;37(1):55–64.PubMedCentralCrossRefPubMed
10.
go back to reference Chen HJ, Kang SP, Lee IJ, Lin YL. Glycyrrhetinic acid suppressed NF-kappaB activation in TNF-alpha-induced hepatocytes. J Agric Food Chem. 2014;62(3):618–25.CrossRefPubMed Chen HJ, Kang SP, Lee IJ, Lin YL. Glycyrrhetinic acid suppressed NF-kappaB activation in TNF-alpha-induced hepatocytes. J Agric Food Chem. 2014;62(3):618–25.CrossRefPubMed
11.
go back to reference Huo HZ, Wang B, Liang YK, Bao YY, Gu Y. Hepatoprotective and antioxidant effects of licorice extract against CCl(4)-induced oxidative damage in rats. Int J Mol Sci. 2011;12(10):6529–43.PubMedCentralCrossRefPubMed Huo HZ, Wang B, Liang YK, Bao YY, Gu Y. Hepatoprotective and antioxidant effects of licorice extract against CCl(4)-induced oxidative damage in rats. Int J Mol Sci. 2011;12(10):6529–43.PubMedCentralCrossRefPubMed
12.
go back to reference Jeong HG, You HJ, Park SJ, Moon AR, Chung YC, Kang SK, et al. Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res. 2002;46(3):221–7.CrossRefPubMed Jeong HG, You HJ, Park SJ, Moon AR, Chung YC, Kang SK, et al. Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res. 2002;46(3):221–7.CrossRefPubMed
13.
go back to reference Teli MR, Day CP, Burt AD, Bennett MK, James OF. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet. 1995;346(8981):987–90.CrossRefPubMed Teli MR, Day CP, Burt AD, Bennett MK, James OF. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet. 1995;346(8981):987–90.CrossRefPubMed
14.
go back to reference Deleuran T, Gronbaek H, Vilstrup H, Jepsen P. Cirrhosis and mortality risks of biopsy-verified alcoholic pure steatosis and steatohepatitis: a nationwide registry-based study. Aliment Pharmacol Ther. 2012;35(11):1336–42.CrossRefPubMed Deleuran T, Gronbaek H, Vilstrup H, Jepsen P. Cirrhosis and mortality risks of biopsy-verified alcoholic pure steatosis and steatohepatitis: a nationwide registry-based study. Aliment Pharmacol Ther. 2012;35(11):1336–42.CrossRefPubMed
15.
go back to reference Haflidadottir S, Jonasson JG, Norland H, Einarsdottir SO, Kleiner DE, Lund SH, et al. Long-term follow-up and liver-related death rate in patients with non-alcoholic and alcoholic related fatty liver disease. BMC Gastroenterol. 2014;14:166.PubMedCentralCrossRefPubMed Haflidadottir S, Jonasson JG, Norland H, Einarsdottir SO, Kleiner DE, Lund SH, et al. Long-term follow-up and liver-related death rate in patients with non-alcoholic and alcoholic related fatty liver disease. BMC Gastroenterol. 2014;14:166.PubMedCentralCrossRefPubMed
16.
go back to reference Yu JY, Ha JY, Kim KM, Jung YS, Jung JC, Oh S. Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver. Molecules. 2015;20(7):13041–54.CrossRefPubMed Yu JY, Ha JY, Kim KM, Jung YS, Jung JC, Oh S. Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver. Molecules. 2015;20(7):13041–54.CrossRefPubMed
17.
go back to reference Neuschwander-Tetri BA, Roll FJ. Glutathione measurement by high-performance liquid chromatography separation and fluorometric detection of the glutathione-orthophthalaldehyde adduct. Anal Biochem. 1989;179(2):236–41.CrossRefPubMed Neuschwander-Tetri BA, Roll FJ. Glutathione measurement by high-performance liquid chromatography separation and fluorometric detection of the glutathione-orthophthalaldehyde adduct. Anal Biochem. 1989;179(2):236–41.CrossRefPubMed
18.
go back to reference Fernandez-Checa JC, Kaplowitz N, Garcia-Ruiz C, Colell A, Miranda M, Mari M, et al. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol. 1997;273(1 Pt 1):G7–17.PubMed Fernandez-Checa JC, Kaplowitz N, Garcia-Ruiz C, Colell A, Miranda M, Mari M, et al. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol. 1997;273(1 Pt 1):G7–17.PubMed
19.
go back to reference Kono H, Rusyn I, Bradford BU, Connor HD, Mason RP, Thurman RG. Allopurinol prevents early alcohol-induced liver injury in rats. J Pharmacol Exp Ther. 2000;293(1):296–303.PubMed Kono H, Rusyn I, Bradford BU, Connor HD, Mason RP, Thurman RG. Allopurinol prevents early alcohol-induced liver injury in rats. J Pharmacol Exp Ther. 2000;293(1):296–303.PubMed
20.
go back to reference Kono H, Arteel GE, Rusyn I, Sies H, Thurman RG. Ebselen prevents early alcohol-induced liver injury in rats. Free Radic Biol Med. 2001;30(4):403–11.CrossRefPubMed Kono H, Arteel GE, Rusyn I, Sies H, Thurman RG. Ebselen prevents early alcohol-induced liver injury in rats. Free Radic Biol Med. 2001;30(4):403–11.CrossRefPubMed
21.
go back to reference Kono H, Rusyn I, Uesugi T, Yamashina S, Connor HD, Dikalova A, et al. Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat. Am J Physiol Gastrointest Liver Physiol. 2001;280(5):G1005–1012.PubMed Kono H, Rusyn I, Uesugi T, Yamashina S, Connor HD, Dikalova A, et al. Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat. Am J Physiol Gastrointest Liver Physiol. 2001;280(5):G1005–1012.PubMed
22.
go back to reference McKim SE, Konno A, Gabele E, Uesugi T, Froh M, Sies H, et al. Cocoa extract protects against early alcohol-induced liver injury in the rat. Arch Biochem Biophys. 2002;406(1):40–6.CrossRefPubMed McKim SE, Konno A, Gabele E, Uesugi T, Froh M, Sies H, et al. Cocoa extract protects against early alcohol-induced liver injury in the rat. Arch Biochem Biophys. 2002;406(1):40–6.CrossRefPubMed
23.
go back to reference Wheeler MD, Kono H, Yin M, Rusyn I, Froh M, Connor HD, et al. Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology. 2001;120(5):1241–50.CrossRefPubMed Wheeler MD, Kono H, Yin M, Rusyn I, Froh M, Connor HD, et al. Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology. 2001;120(5):1241–50.CrossRefPubMed
24.
go back to reference Wheeler MD, Nakagami M, Bradford BU, Uesugi T, Mason RP, Connor HD, et al. Overexpression of manganese superoxide dismutase prevents alcohol-induced liver injury in the rat. J Biol Chem. 2001;276(39):36664–72.CrossRefPubMed Wheeler MD, Nakagami M, Bradford BU, Uesugi T, Mason RP, Connor HD, et al. Overexpression of manganese superoxide dismutase prevents alcohol-induced liver injury in the rat. J Biol Chem. 2001;276(39):36664–72.CrossRefPubMed
25.
go back to reference Kim SJ, Lee JW, Jung YS, Kwon do Y, Park HK, Ryu CS, et al. Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice. J Hepatol. 2009;50(6):1184–91.CrossRefPubMed Kim SJ, Lee JW, Jung YS, Kwon do Y, Park HK, Ryu CS, et al. Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice. J Hepatol. 2009;50(6):1184–91.CrossRefPubMed
26.
go back to reference Bode C, Bode JC. Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res. 2005;29(11 Suppl):166S–71S.CrossRefPubMed Bode C, Bode JC. Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res. 2005;29(11 Suppl):166S–71S.CrossRefPubMed
27.
go back to reference Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology. 2003;124(3):778–90.CrossRefPubMed Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology. 2003;124(3):778–90.CrossRefPubMed
28.
29.
go back to reference Hardardottir I, Doerrler W, Feingold KR, Grunfeld C. Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism. Biochem Biophys Res Commun. 1992;186(1):237–43.CrossRefPubMed Hardardottir I, Doerrler W, Feingold KR, Grunfeld C. Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism. Biochem Biophys Res Commun. 1992;186(1):237–43.CrossRefPubMed
30.
go back to reference Nachiappan V, Curtiss D, Corkey BE, Kilpatrick L. Cytokines inhibit fatty acid oxidation in isolated rat hepatocytes: synergy among TNF, IL-6, and IL-1. Shock. 1994;1(2):123–9.CrossRefPubMed Nachiappan V, Curtiss D, Corkey BE, Kilpatrick L. Cytokines inhibit fatty acid oxidation in isolated rat hepatocytes: synergy among TNF, IL-6, and IL-1. Shock. 1994;1(2):123–9.CrossRefPubMed
31.
go back to reference Endo M, Masaki T, Seike M, Yoshimatsu H. TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med. 2007;232(5):614–21. Endo M, Masaki T, Seike M, Yoshimatsu H. TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med. 2007;232(5):614–21.
32.
go back to reference Yin M, Wheeler MD, Kono H, Bradford BU, Gallucci RM, Luster MI, et al. Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology. 1999;117(4):942–52.CrossRefPubMed Yin M, Wheeler MD, Kono H, Bradford BU, Gallucci RM, Luster MI, et al. Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology. 1999;117(4):942–52.CrossRefPubMed
Metadata
Title
Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease
Authors
Jae-Chul Jung
Yun-Hee Lee
Sou Hyun Kim
Keuk-Jun Kim
Kyung-Mi Kim
Seikwan Oh
Young-Suk Jung
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-0997-0

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