Inhibition of liver X receptor-α-dependent hepatic steatosis by isoliquiritigenin, a licorice antioxidant flavonoid, as mediated by JNK1 inhibition

Free Radical Biology and Medicine

Volumn 49, Issue 11, 2010, Pages 1722-1734

  Kim, Young Mi ^a   Kim, Tae Hyun ^a   Kim, Young Woo ^a   Yang, Yoon Mee ^a   Ryu, Da Hye ^b   Hwang, Se Jin ^b   Lee, Jong Rok ^c   Kim, Sang Chan ^c   Kim, Sang Geon ^a  

^a Seoul National University   (South Korea)

^b Hanyang University   (South Korea)

^c Daegu Haany University   (South Korea)

Author keywords

Free radicals; Hepatic steatosis; High fat diet; Isoliquiritigenin; JNK1 inhibition; LXR ; Oxidative stress

Indexed keywords

ABC TRANSPORTER A1; ACETYL COENZYME A CARBOXYLASE; ACTIN; ACYL COENZYME A DESATURASE; CYCLOOXYGENASE 2; FAT; FATTY ACID SYNTHASE; INDUCIBLE NITRIC OXIDE SYNTHASE; ISOLIQUIRITIGENIN; LIVER X RECEPTOR ALPHA; MITOGEN ACTIVATED PROTEIN KINASE KINASE 7; MITOGEN ACTIVATED PROTEIN KINASE P38; N (2,2,2 TRIFLUOROETHYL) N [4 [2,2,2 TRIFLUORO 1 HYDROXY 1 (TRIFLUOROMETHOXY)ETHYL]PHENYL]BENZENESULFONAMIDE; PALMITIC ACID; SERINE; STEAROYL COENZYME A DESATURASE 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; STRESS ACTIVATED PROTEIN KINASE 1; THIOBARBITURIC ACID REACTIVE SUBSTANCE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; BLOOD CHEMISTRY; CONTROLLED STUDY; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FATTY LIVER; GLYCYRRHIZA; HISTOPATHOLOGY; HUMAN; HUMAN CELL; LIPOGENESIS; LIVER INJURY; LIVER PROTECTION; MALE; MOUSE; NITROTYROSINYLATION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; RECEPTOR DOWN REGULATION; RECEPTOR UPREGULATION;

ANIMALS; ANTIOXIDANTS; CELLS, CULTURED; CHALCONES; DRUG EVALUATION, PRECLINICAL; FATTY LIVER; FLAVONOIDS; GLYCYRRHIZA; HEP G2 CELLS; HUMANS; LIPOGENESIS; MALE; MICE; MICE, INBRED C57BL; MITOGEN-ACTIVATED PROTEIN KINASE 8; MODELS, BIOLOGICAL; ORPHAN NUCLEAR RECEPTORS; PROTEIN KINASE INHIBITORS; TRANSCRIPTION, GENETIC;

GLYCYRRHIZA; MUS;

EID: 78049384496     PISSN: 08915849     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2010.09.001     Document Type: Article

References (50)

1. Zelcer N., Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J. Clin. Invest. 2005, 116:607-614.
2. Repa J.J., Liang G., Ou J., Bashmakov Y., Lobaccaro J.M., Shimomura I. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000, 14:2819-2830.
3. Steffensen K.R., Gustafsson J.A. Putative metabolic effects of the liver X receptor (LXR). Diabetes 2004, 53(Suppl. 1):S36-S42.
4. Zhou J., Febbraio M., Wada T., Zhai Y., Kuruba R., He J., Lee J.H., Khadem S., Ren S., Li S., Silverstein R.L., Xie W. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology 2008, 134:556-567.
5. Mantena S.K., King A.L., Andringa K.K., Eccleston H.B., Bailey S.M. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic. Biol. Med. 2008, 44:1259-1272.
6. Mantena S.K., Vaughn D.P., Andringa K.K., Eccleston H.B., King A.L., Abrams G.A., Doeller J.E., Kraus D.W., Darley-Usmar V.M., Bailey S.M. High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem. J. 2009, 417:183-193.
7. Abdelmalek M., Angulo P., Jorgensen R.A., Sylvestre P., Lindor K.D. Betaine, a promising new agent for patients with non-alcoholic steatohepatitis: results of a pilot study. Am. J. Gastroenterol. 2001, 96:2711-2717.
8. Geoffrey C.F., Claire Z.L. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006, 43:S99-S112.
9. Lavine J.E. Vitamin E treatment of non-alcoholic steatohepatitis in children: a pilot study. J. Pediatr. 2000, 136:734-738.
10. Carmiel-Haggai M., Cederbaum A.I., Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 2005, 19:136-138.
11. Haraguchi H., Ishikawa H., Mizutani K., Tamura Y., Kinoshita T. Antioxidative and superoxide scavenging activities of retrochalcones in Glycyrrhiza inflata. Bioorg. Med. Chem. 1998, 6:339-347.
12. Chin Y.W., Jung H.A., Liu Y., Su B.N., Castoro J.A., Keller W.J., Pereira M.A., Kinghorn A.D. Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). J. Agric. Food Chem. 2007, 55:4691-4697.
13. Kumar S., Sharma A., Madan B., Singhal V., Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells. Biochem. Pharmacol. 2007, 73:1602-1612.
14. Kim J.Y., Park S.J., Yun K.J., Cho Y.W., Park H.J., Lee K.T. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-κB in Raw264.7 macrophages. Eur. J. Pharmacol. 2008, 584:175-184.
15. Lee S.H., Kim J.Y., Seo G.S., Kim Y.C., Sohn D.H. Isoliquiritigenin, from Dalbergia odorifera, up-regulates anti-inflammatory heme oxygenase-1 expression in Raw264.7 macrophages. Inflammation Res. 2009, 58:257-262.
16. Ii T., Satomi Y., Katoh D., Shimada J., Baba M., Okuyama T., Nishino H., Kitamura N. Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett. 2004, 207:27-35.
17. Yamazaki S., Morita T., Endo H., Hamamoto T., Baba M., Joichi Y., Kaneko S., Okada Y., Okuyama T., Nishino H., Tokue A. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett. 2002, 183:23-30.
18. Lee Y.M., Lim D.Y., Choi H.J., Jung J.I., Chung W.Y., Park J.H. Induction of cell cycle arrest in prostate cancer cells by the dietary compound isoliquiritigenin. J. Med. Food 2009, 12:8-14.
19. Lee C.K., Son S.H., Park K.K., Park J.H., Lim S.S., Chung W.Y. Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma. J. Pharmacol. Sci. 2008, 106:444-451.
20. Choi S.H., Kim Y.W., Kim S.G. AMPK-mediated GSK3beta inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress. Biochem. Pharmacol. 2010, 79:1352-1362.
21. Singh R., Wang Y., Xiang Y., Tanaka K.E., Gaarde W.A., Czaja M.J. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology 2009, 49:87-96.
22. Schattenberg J.M., Singh R., Wang Y., Lefkowitch J.H., Rigoli R.M., Scherer P.E., Czaja M.J. JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 2006, 43:163-172.
23. Hirosumi J., Tuncman G., Chang L., Görgün C.Z., Uysal K.T., Maeda K., Karin M., Hotamisligil G.S. A central role for JNK in obesity and insulin resistance. Nature 2002, 420:333-336.
24. Jang E.Y., Choe E.S., Hwang M., Kim S.C., Lee J.R., Kim S.G., Jeon J.P., Buono R.J., Yang C.H. Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABA(B) receptor. Eur. J. Pharmacol. 2008, 587:124-128.
25. Wadsworth S.J., Gebauer G., van Rossum G.D., Dhanasekaran N. Ras-dependent signaling by the GTPase-deficient mutant of Galpha12. J. Biol. Chem. 1997, 272:28829-28832.
26. Coso O.A., Chiariello M., Yu J.C., Teramoto H., Crespo P., Xu N., Miki T., Gutkind J.S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 1995, 81:1137-1146.
27. Choi H.S., Bode A.M., Shim J.H., Lee S.Y., Dong Z. c-Jun N-terminal kinase 1 phosphorylates Myt1 to prevent UVA-induced skin cancer. Mol. Cell. Biol. 2009, 29:2168-2180.
28. Hwahng S.H., Ki S.H., Bae E.J., Kim H.E., Kim S.G. Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones. Hepatology 2009, 49:1913-1925.
29. Mollica M.P., Lionetti L., Moreno M., Lombardi A., De Lange P., Antonelli A. 3, 5-Diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet. J. Hepatol. 2009, 51:363-570.
30. Inoue M., Ohtake T., Motomura W., Takahashi N., Hosoki Y., Miyoshi S. Increased expression of PPAR? in high fat diet-induced liver steatosis in mice. Biochem. Biophys. Res. Commun. 2005, 336:215-222.
31. Kim Y.W., Kang H.E., Lee M.G., Hwang S.E., Kim S.C., Lee C.H., Kim S.G. Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase II enzymes. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296:G372-G381.
32. Laffitte B.A., Joseph S.B., Walczak R., Pei L., Wilpitz D.C., Collins J.L., Tontonoz P. Autoregulation of the human liver X receptor alpha promoter. Mol. Cell. Biol. 2001, 21:7558-7568.
33. Bonnard C., Durand A., Peyrol S., Chanseaume E., Chauvin M.A., Morio B. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J. Clin. Invest. 2008, 118:789-800.
34. Hu W., Bielawski J., Samad F., Merrill A.H., Cowart L.A. Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity. J. Lipid Res. 2009, 50:1852-1862.
35. Kwon G.T., Cho H.J., Chung W.Y., Park K.K., Moon A., Park J.H. Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J. Nutr. Biochem. 2009, 20:663-676.
36. Kang S.W., Choi J.S., Choi Y.J., Bae J.Y., Li J., Kim D.S., Kim J.L., Shin S.Y., Lee Y.J., Kwun I.S., Kang Y.H. Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK-responsive signaling pathways leading to induction of matrix metalloproteinases. J. Nutr. Biochem. 2009, 21:55-65.
37. Hotamisligil G.S., Arner P., Caro J.F., Atkinson R.L., Spiegelman B.M. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 1995, 95:2409-2415.
38. Crespo J., Cayón A., Fernández-Gil P., Hernández-Guerra M., Mayorga M., Domínguez-Díez A., Fernández-Escalante J.C., Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001, 34:1158-1163.
39. Chen M., Bradley M.N., Beaven S.W., Tontonoz P. Phosphorylation of the liver X receptors. FEBS Lett. 2006, 580:4835-4841.
40. Kim Y.W., Kim Y.M., Yang Y.M., Kim T.H., Hwang S.J., Lee J.R., Kim S.C., Kim S.G. Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis. Free Radic. Biol. Med. 2010, 48:567-578.
41. Luo Y., Eggler A.L., Liu D., Liu G., Mesecar A.D., van Breemen R.B. Sites of alkylation of human Keap1 by natural chemoprevention agents. J. Am. Soc. Mass Spectrom. 2007, 18:2226-2232.
42. Eggler A.L., Liu G., Pezzuto J.M., van Breemen R.B., Mesecar A.D. Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc. Natl Acad. Sci. USA 2005, 102:10070-10075.
43. Marchesini G., Brizi M., Bianchi G., Tomassetti S., Bugianesi E., Lenzi M., McCullough A.J., Natale S., Forlani G., Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001, 50:1844-1850.
44. Joseph S.B., Laffitte B.A., Patel P.H., Watson M.A., Matsukuma K.E., Walczak R. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J. Biol. Chem. 2002, 277:11019-11025.
45. Kodama Y., Brenner D.A. c-Jun N-terminal kinase signaling in the pathogenesis of nonalcoholic fatty liver disease: multiple roles in multiple steps. Hepatology 2009, 49:6-8.
46. Kapil M., David H.T., Nikunj S., Sohrab M. Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutr. Rev. 2002, 60:289-293.
47. 2-terminal kinase activation and elevated proapoptotic Bax. J. Nutr. 2008, 138:1866-1871.
48. Guo J., Liu D., Nikolic D., Zhu D., Pezzuto J.M., van Breemen R.B. In vitro metabolism of isoliquiritigenin by human liver microsomes. Drug Metab. Dispos. 2008, 36:461-468.
49. Guo J., Liu A., Cao H., Luo Y., Pezzuto J.M., van Breemen R.B. Biotransformation of the chemopreventive agent 2′, 4′, 4-trihydroxychalcone (isoliquiritigenin) by UDP-glucuronosyltransferases. Drug Metab. Dispos. 2008, 36:2104-2112.
50. Cuendet M., Guo J., Luo Y., Chen S., Oteham C.P., Moon R.C., van Breemen R.B., Marler L.E., Pezzuto J.M. Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice. Cancer Prev. Res. 2010, 3:221-232.