Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
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Fermented Ginseng Attenuates Hepatic Lipid Accumulation and Hyperglycemia through AMPK Activation

  • Kim, Do-Yeon (Department of Life and Nanopharmaceutical and Department of Pharmaceutical Science, Kyung Hee University) ;
  • Park, Jong-Seok (Department of Life and Nanopharmaceutical and Department of Pharmaceutical Science, Kyung Hee University) ;
  • Yuan, Hai-Dan (Department of Life and Nanopharmaceutical and Department of Pharmaceutical Science, Kyung Hee University) ;
  • Chung, Sung-Hyun (Department of Life and Nanopharmaceutical and Department of Pharmaceutical Science, Kyung Hee University)
  • Published : 2009.02.28
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Abstract

Fermented ginseng (FG) is an ethanol extract of ginseng radix processed with $\beta$-galactosidase. It was hypothesized that FG may exert anti-hyperlipidemic and anti-diabetic activities through modulating AMP-activated protein kinase (AMPK) in HepG2 human hepatoma cells. In this study, we showed that AMPK phosphorylation was stimulated by FG. These effects were abolished by pretreatment with an AMPK inhibitor, compound C. In addition, FG regulated the expression of genes associated with lipogenesis and lipolysis, thus causing suppression of hepatic triglyceride accumulation. In vivo study using db/db mice, FG reduced fasting plasma glucose, HbAlc, and insulin resistance index, when compared to diabetic control. FG also increased the phospho-AMPK and glucose transporter 4 (GLUT4) expressions in liver and skeletal muscle, respectively. In liver, expressions of lipogenic gene were decreased whereas expressions of lipolytic genes were induced, when compared to diabetic control. Taken together, we may suggest that FG ameliorates hyperglycemia and hyperlipidemia through activation of AMPK and could be developed as a health functional food or therapeutic agent for type 2 diabetic patients.

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References

  1. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 21: S5-S19 (1998) https://doi.org/10.2337/diacare.21.1.S5
  2. Ferrannini E. Insulin resistance versus insulin deficiency in noninsulin-dependent diabetes mellitus: Problems and prospects. Endocro. Rev. 19: 477-490 (1998) https://doi.org/10.1210/er.19.4.477
  3. Gerich JE. The genetic basis of type 2 diabetes mellitus: Impaired insulin secretion versus impaired insulin sensitivity. Endocro. Rev. 19:491-503(1998) https://doi.org/10.1210/er.19.4.491
  4. Weickert MO, Pfeiffer AFH. Signaling mechanisms linking hepatic glucose and lipid metabolism. Diabetologia 49: 1732-1741 (2006) https://doi.org/10.1007/s00125-006-0295-3
  5. Hardie DG, Carling D. The AMPK-activated protein kinase: Fuel gauge of mammalian cells. Eur. J. Biochem. 246: 259-273 (1998)
  6. Hardie DG, Carling D, Scott JW, Pan ER, Hudson ER. The AMP-activated/SNF protein kinase subfamily: Metabolic sensors of the eukaryotic cell? Annu. Rev. Biochem. 67: 821-855 (1998) https://doi.org/10.1146/annurev.biochem.67.1.821
  7. Hardie DG, Scott JW, Pan DA, Hudson ER. Management of cellular energy by energy by the AMP-activated protein kinase system. FEBS Lett. 546: 113-120 (2003) https://doi.org/10.1016/S0014-5793(03)00560-X
  8. Hardie DH, Carling D. The AMP-activated protein kinase. Fuel gauge of the mammalian cell? Eur. J. Biochem. 246: 259-273 (1997) https://doi.org/10.1111/j.1432-1033.1997.00259.x
  9. Hardie DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell? Annu. Rev. Biochem. 67: 821-855 (1998) https://doi.org/10.1146/annurev.biochem.67.1.821
  10. Han GC, Ko SK, Sung JH, Chung SH. Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice. J. Agr. Food Chem. 55: 10641-10648 (2007) https://doi.org/10.1021/jf0722598
  11. Park MW, Ha JI, Chung SH. 20(S)-Ginsenoside $Rg_3$ enhances glucose-stimulated insulin secretion and activates AMPK. BioI. Parm. Bull. 31: 748-751 (2008) https://doi.org/10.1248/bpb.31.748
  12. Vuksan V, Sievenpiper JL. Herbal remedies in the management of diabetes: Lessons learned from the study of ginseng. Nutr. Metab. Cardiovas. 15: 149-160 (2005) https://doi.org/10.1016/j.numecd.2005.05.001
  13. Han KL, Jung MH, Sohn JH, Hwang JK. Ginsenoside 20 (S)-protopanaxatriol (PPT) activates peroxisome proliferator-activated receptor $\gamma$ (PPAR$\gamma$) in 3T3-Ll adipocytes. BioI. Pharm. Bull. 29:110-113 (2006) https://doi.org/10.1248/bpb.29.110
  14. Shang W, Yang Y, Jiang B, Jin H, Zhou L, Liu S, Chen M. Ginsenoside $Rb_1$ promotes adipogenesis in 3T3-L1 cells by enhancing $PPAR{\gamma}_2$ and CIEBP$\alpha$ gene expression. Life Sci. 80: 618-625 (2007) https://doi.org/10.1016/j.lfs.2006.10.021
  15. Lau AJ, WooSO, Koh HL. Analysis of sap on ins in raw and steamed Ranax notoginseng using high-performance liquid chromatography with diode array detection. J. Chromatogr. A 1011:77-87 (2003) https://doi.org/10.1016/S0021-9673(03)01135-X
  16. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Peroxisome-proliferator-activated receptor $\delta$ activates fat metabolism to prevent obesity. Cell 113: 159-170 (2003) https://doi.org/10.1016/S0092-8674(03)00269-1
  17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turne RL. Homeostasis model assessment insulin resistance and beta-cell function form fasting plasma glucose and insulin concentration in man. Diabetologia 28: 412-419 (1985) https://doi.org/10.1007/BF00280883
  18. Akli S, Chelly J, Lacorte JM, Poenaru L, Kahn A. Seven novel Tay-Sachs mutateions detected by chemical mismatch cleavage of PCR-amplified cDNA fragments. Genomics 11: 124-134 (1991) https://doi.org/10.1016/0888-7543(91)90109-R
  19. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, Hue L, Andreelli F. Activation of AMP-activated protein kinase in the liver: A new strategy for the management of metabolic hepatic disorders. J. Physiol. 574: 41-53 (2006) https://doi.org/10.1113/jphysiol.2006.108506
  20. Hardie DG. The AMP-activated protein kinase pathway-new players upstream and downstream. J. Cell Sci. 117: 5479-5487 (2004) https://doi.org/10.1242/jcs.01540
  21. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenky-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Gppduer LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108: 1167-1174 (2001) https://doi.org/10.1172/JCI13505
  22. Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, Aguilar Contreras A, Contreras-Weber CC, Flores-Saenz JL. Study of the anti-hyperglycemic effect of plants used as antidiabetics. J. Ethnopharmacol. 61: 101-110 (1998) https://doi.org/10.1016/S0378-8741(98)00020-8
  23. Birnbaum MJ. Activating AMP-activated protein kinase without AMP. Mol. Cell 19: 289-290 (2005) https://doi.org/10.1016/j.molcel.2005.07.012
  24. Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB 1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310: 1642-1646 (2005) https://doi.org/10.1126/science.1120781
  25. Moller DE, Kaufman KD. Metabolic syndrome: A clinical and molecular perspective. Annu. Rev. Med. 56: 45-62 (2005) https://doi.org/10.1146/annurev.med.56.082103.104751
  26. Yamauch T, Kamon J, Waki H, Teruchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Retman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7: 941-953 (2001) https://doi.org/10.1038/90984