Honokiol activates the LKB1-AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

Toxicology and Applied Pharmacology

Volumn 284, Issue 2, 2015, Pages 113-124

  Seo, Min Suk ^a   Kim, Jung Hwan ^a   Kim, Hye Jung ^a   Chang, Ki Churl ^a   Park, Sang Won ^a  

^a Gyeongsang National University School of Medicine   (South Korea)

Author keywords

Adenosine monophosphate activated protein kinase; Hepatocytes; Honokiol; Lipogenesis; Liver kinase b1; Non alcoholic steatosis

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ACYL COENZYME A DESATURASE; BIPHENYL DERIVATIVE; FATTY ACID; FATTY ACID SYNTHASE; HONOKIOL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LIGNAN; PROTEIN SERINE THREONINE KINASE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIACYLGLYCEROL;

ANIMAL; C57BL MOUSE; CYTOLOGY; DRUG EFFECTS; HEPG2 CELL LINE; HUMAN; LIPID DIET; LIPID METABOLISM; LIPOGENESIS; LIVER; LIVER CELL; MALE; METABOLISM; MOUSE; PHOSPHORYLATION; PROCEDURES; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ACETYL-COA CARBOXYLASE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; BIPHENYL COMPOUNDS; CELL LINE, TUMOR; DIET, HIGH-FAT; FATTY ACID SYNTHASES; FATTY ACIDS, NONESTERIFIED; HEP G2 CELLS; HEPATOCYTES; HUMANS; LIGNANS; LIPID METABOLISM; LIPOGENESIS; LIVER; MALE; MICE; MICE, INBRED C57BL; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; STEAROYL-COA DESATURASE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIGLYCERIDES;

EID: 84932109091     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2015.02.020     Document Type: Article

References (34)

1. Arora S., Singh S., Piazza G.A., Contreras C.M., Panyam J., Singh A.P. Honokiol: a novel natural agent for cancer prevention and therapy. Curr. Mol. Med. 2012, 12:1244-1252.
2. Bai T., Yang Y., Wu Y.L., Jiang S., Lee J.J., Lian L.H., Nan J.X. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. Int. Immunopharmacol. 2014, 19:351-357.
3. Bar-Sela G., Epelbaum R., Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr. Med. Chem. 2010, 17:190-197.
4. Browning J.D., Horton J.D. Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest. 2004, 114:147-152.
5. Chakrabarti P., English T., Karki S., Qiang L., Tao R., Kim J., Luo Z., Farmer S.R., Kandror K.V. SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. J. Lipid Res. 2011, 52:1693-1701.
6. Chen F., Wang T., Wu Y.F., Gu Y., Xu X.L., Zheng S., Hu X. Honokiol: a potent chemotherapy candidate for human colorectal carcinoma. World J. Gastroenterol. 2004, 10:3459-3463.
7. Donnelly K.L., Smith C.I., Schwarzenberg S.J., Jessurun J., Boldt M.D., Parks E.J. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Invest. 2005, 115:1343-1351.
8. Dowman J.K., Tomlinson J.W., Newsome P.N. Pathogenesis of non-alcoholic fatty liver disease. QJM 2010, 103:71-83.
9. Gomez-Lechon M.J., Donato M.T., Martinez-Romero A., Jimenez N., Castell J.V., O'Connor J.E. A human hepatocellular in vitro model to investigate steatosis. Chem. Biol. Interact. 2007, 165:106-116.
10. Griffin M.J., Wong R.H., Pandya N., Sul H.S. Direct interaction between USF and SREBP-1c mediates synergistic activation of the fatty-acid synthase promoter. J. Biol. Chem. 2007, 282:5453-5467.
11. Gutierrez-Juarez R., Pocai A., Mulas C., Ono H., Bhanot S., Monia B.P., Rossetti L. Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance. J. Clin. Invest. 2006, 116:1686-1695.
12. Ha J., Daniel S., Broyles S.S., Kim K.H. Critical phosphorylation sites for acetyl-CoA carboxylase activity. J. Biol. Chem. 1994, 269:22162-22168.
13. Horton J.D., Goldstein J.L., Brown M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 2002, 109:1125-1131.
14. Hou X., Xu S., Maitland-Toolan K.A., Sato K., Jiang B., Ido Y., Lan F., Walsh K., Wierzbicki M., Verbeuren T.J., Cohen R.A., Zang M. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J. Biol. Chem. 2008, 283:20015-20026.
15. Hudgins L.C., Hellerstein M.K., Seidman C.E., Neese R.A., Tremaroli J.D., Hirsch J. Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects. J. Lipid Res. 2000, 41:595-604.
16. Hur W., Kim S.W., Lee Y.K., Choi J.E., Hong S.W., Song M.J., Bae S.H., Park T., Um S.J., Yoon S.K. Oleuropein reduces free fatty acid-induced lipogenesis via lowered extracellular signal-regulated kinase activation in hepatocytes. Nutr. Res. 2012, 32:778-786.
17. Kim Y.W., Lee S.M., Shin S.M., Hwang S.J., Brooks J.S., Kang H.E., Lee M.G., Kim S.C., Kim S.G. Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury. Free Radic. Biol. Med. 2009, 47:1082-1092.
18. Kim Y.J., Choi M.S., Cha B.Y., Woo J.T., Park Y.B., Kim S.R., Jung U.J. Long-term supplementation of honokiol and magnolol ameliorates body fat accumulation, insulin resistance, and adipose inflammation in high-fat fed mice. Mol. Nutr. Food Res. 2013, 57:1988-1998.
19. Lee Y.J., Lee Y.M., Lee C.K., Jung J.K., Han S.B., Hong J.T. Therapeutic applications of compounds in the Magnolia family. Pharmacol. Ther. 2011, 130:157-176.
20. Lee J.H., Jung J.Y., Jang E.J., Jegal K.H., Moon S.Y., Ku S.K., Kang S.H., Cho I.J., Park S.J., Lee J.R., Zhao R.J., Kim S.C., Kim Y.W. Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK-SREBP-1 c pathway. Exp. Biol. Med. (Maywood) 2014.
21. Lin J.W., Chen J.T., Hong C.Y., Lin Y.L., Wang K.T., Yao C.J., Lai G.M., Chen R.M. Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway. Neuro Oncol. 2012, 14:302-314.
22. Mao J., DeMayo F.J., Li H., Abu-Elheiga L., Gu Z., Shaikenov T.E., Kordari P., Chirala S.S., Heird W.C., Wakil S.J. Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:8552-8557.
23. Mendez-Sanchez N., Arrese M., Zamora-Valdes D., Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int. 2007, 27:423-433.
24. Musso G., Gambino R., Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog. Lipid Res. 2009, 48:1-26.
25. Nagalingam A., Arbiser J.L., Bonner M.Y., Saxena N.K., Sharma D. Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Res. 2012, 14:R35.
26. Neuschwander-Tetri B.A., Caldwell S.H. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003, 37:1202-1219.
27. Niu Y., Li S., Na L., Feng R., Liu L., Li Y., Sun C. Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK. PLoS One 2012, 7:e30782.
28. Park E.J., Zhao Y.Z., Na M., Bae K., Kim Y.H., Lee B.H., Sohn D.H. Protective effects of honokiol and magnolol on tertiary butyl hydroperoxide- or d-galactosamine-induced toxicity in rat primary hepatocytes. Planta Med. 2003, 69:33-37.
29. Postic C., Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest. 2008, 118:829-838.
30. Purushotham A., Schug T.T., Xu Q., Surapureddi S., Guo X., Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009, 9:327-338.
31. Stein S.C., Woods A., Jones N.A., Davison M.D., Carling D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem. J. 2000, 345(Pt 3):437-443.
32. Wu C.H., Ou T.T., Chang C.H., Chang X.Z., Yang M.Y., Wang C.J. The polyphenol extract from Sechium edule shoots inhibits lipogenesis and stimulates lipolysis via activation of AMPK signals in HepG2 cells. J. Agric. Food Chem. 2014, 62:750-759.
33. Yin H.Q., Kim Y.C., Chung Y.S., Kim Y.C., Shin Y.K., Lee B.H. Honokiol reverses alcoholic fatty liver by inhibiting the maturation of sterol regulatory element binding protein-1c and the expression of its downstream lipogenesis genes. Toxicol. Appl. Pharmacol. 2009, 236:124-130.
34. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., Moller D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 2001, 108:1167-1174.