DOI QR코드

DOI QR Code

The Ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions

  • Kim, Eun-Ju (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Lee, Hyun-Il (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Chung, Kyung-Jin (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Noh, Yun-Hee (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Ro, Young-Tae (Department of Biochemistry, School of Medicine, Konkuk University) ;
  • Koo, Ja-Hyun (Department of Biochemistry, School of Medicine, Konkuk University)
  • Published : 2009.04.30

Abstract

The effects of the ginsenoside Rb2 (Rb2) on lipid metabolism were characterized in 3T3-L1 adipocytes to evaluate their utility for treating obesity. While the amounts of total cholesterol and triacylglycerol (TAG) were markedly increased in the adipocytes treated with high amounts of cholesterol and fetal bovine serum (FBS), the test groups treated with Rb2 showed levels that were close to normal. The effect of Rb2 on these cells was comparable to that of lovastatin. Rb2 enhanced the expression of the sterol regulated element binding protein (SREBP) mRNA whereas treatment with cholesterol and FBS led to a reduction in the abundance of this transcript. The activity of fatty acid synthetase (FAS) was lower in the cholesterol group compared to the Rb2 treatment group suggesting that the observed decrease in cholesterol levels and activated SREBP was mediated by Rb2. Treatment with Rb2 also resulted in a decrease in TAG levels in adipocytes cultured under high fatty acid conditions. This effect was mediated by stimulating the expression of SREBP and Leptin mRNA, suggesting that Rb2 might be a valuable component capable of lowering the levels of lipids.

Keywords

References

  1. Shibata, S. (1977) New natural products and plant drugs with pharmacological, biological or therapeutical activity. Wagner, H. and Wolff, P., (eds.) pp. 177-196. Springer-Verlag, Berlin
  2. Yamamoto, M., Uemura, T., Nakama, S., Uemiya, M. and Kumagai, A. (1983) Serum HDL-cholesterol-increasing and fatty liver-improving actions of panax ginseng in high cholesterol diet-fed rats with clinical effect on hyperlipidemia in man. Am. J. Chin. Med. 11, 96-101 https://doi.org/10.1142/S0192415X83000161
  3. Yamamoto, M., Kumagai, A. and Yamamura, Y. (1983) Plasma lipid-lowering action of ginseng saponins and mechanism of the action. Am. J. Chin. Med. 11, 84-87 https://doi.org/10.1142/S0192415X83000148
  4. Ikehara, M., Shibata, Y., Higashi, T., Sanada, S. and Shoji, J. (1978) Effect of ginseng saponins on cholesterol metabolism. III. Effect of ginsenoside-Rb1 on cholesterol synthesis in rats fed on high-fat diet. Chem. Pharm. Bull. 26, 284-285
  5. Lim, G., Lee, H. I, Kim, E. J., Noh, Y. H., Ro, Y. T. and Koo, J. H. (2005) Ginsenoside Rb2 upregulates the low density lipoprotein receptor gene expression through the activation of the sterol regulated element binding protein maturation in HepG2 cells. J. Ginseng Res. 29, 159-166 https://doi.org/10.5142/JGR.2005.29.4.159
  6. Sakai, J., Rawson, R. B., Espenshade, P. J., Cheng, D., Seegmiller, A. C., Goldstein, J. L. and Brown, M. S. (1998) Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells. Molecular Cell 2, 505-514 https://doi.org/10.1016/S1097-2765(00)80150-1
  7. Edwards, P. A., Tabor, D., Kast, H. R. and Venkateswaran, A. (2000) Regulation of gene expression by SREBP and SCAP. Biochimica et Biophysica Acta 1529, 103-113 https://doi.org/10.1016/S1388-1981(00)00140-2
  8. Eberle, D., Hegarty, B., Bossard, P., Ferre P. and Foufelle, F. (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 86, 839-848 https://doi.org/10.1016/j.biochi.2004.09.018
  9. Magana, M. M. and Osborne, T. F. (1996) Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. J. Biol. Chem. 271, 32689-32694 https://doi.org/10.1074/jbc.271.51.32689
  10. Magana, M. M., Lin, S. S., Dooley, K. A. and Osborne, T. F. (1997) Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins. J. Lipid Res. 38, 1630-1638
  11. Ericsson, J., Jackson, S. M., Kim, J. B., Spiegelmanm, B. M. and Edwards, P. A. (1997) Identification of Glycerol-3-phosphate acyltransferase as an adipocyte determination and differentiation factor 1-and sterol regulatory elementbinding protein-responsive gene. J. Biol. Chem. 272, 7298-7305 https://doi.org/10.1074/jbc.272.11.7298
  12. Li, J. N., Mahmoud, M. A., Han, W. F., Ripple, M. and Pizer, E. S. (2000) Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia. Experimental Cell Research 261, 159-165 https://doi.org/10.1006/excr.2000.5054
  13. Spiegelman, B. M. and Flier, J. S. (1996) Adipogenesis and obesity: rounding out the big picture. Cell 87, 377-389 https://doi.org/10.1016/S0092-8674(00)81359-8
  14. Juge-Aubry, C. E., Henrichot, E. and Meier, C. A. (2005) Adipose tissue: a regulator of inflammation. Best Pract. Res. Clin. Endocrinol Metab. 19, 547-66 https://doi.org/10.1016/j.beem.2005.07.009
  15. Yokazawa, T., Yasui, T. and Oura, H. (1993) Effects of ginsenoside-Rb2 on RNA synthesis. Phytotheraphy 7, 68 https://doi.org/10.1002/ptr.2650070116
  16. Yoo, K. J., Lee, K. Y. and Lee, S. K. (1990) Inductive effects of ginseng saponins on the rat LDH gene and the synthetic rate of hepatocyte DNA in generating liver cells. Korean J. Ginseng Sci. 14, 200
  17. Boizard, M., Liepvre, X. L., Lemarchand, P., Foufelle, F., Ferre, P. and Dugail, I. (1998) Obesity-related overexpression of fatty-acid synthase gene in adipose tissue involves sterol regulatory element-binding protein transcription factors. J. Biol. Chem. 273, 29164-29171 https://doi.org/10.1074/jbc.273.44.29164
  18. Foufelle, F., Gouhot, B., Pegorier, J. P., Perdereau, D., Girard, J. and Ferre, P. (1992) Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. J. Biol. Chem. 267, 20543-20546
  19. Paulauskis, J. D. and Sul, H. S. (1989) Hormonal regulation of mouse fatty acid synthase gene transcription in liver. J. Biol. Chem. 264, 574-577
  20. Stapleton, S. R., Mitchell, D. A., Salati, L. M. and Goodeidge, A. G. (1990) Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick embryo hepatocytes in culture. Insulin and insulin-like growth factor amplify that effect. J. Biol. Chem. 265, 18442-18446
  21. Bennett, M. K., Lopez, J. M., Sanchez, H. B. and Osborne, T. F. (1995) Sterol regulation of fatty acid synthase promoter. J. Biol. Chem. 270, 25578-25583 https://doi.org/10.1074/jbc.270.43.25578
  22. Sottile ,V. and Seuwen, K. (2001) A high-capacity screen for adipogenic differntiation. Analytical Biochemistry 293, 124-128 https://doi.org/10.1006/abio.2001.5121
  23. Voehringer, D. W., Hirschberg, D. L., Xiao, J., Lu, Q., Roederer, M., Lock, C. N., Steinman, L. and Herzenberg, L. A. (2000) Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proc. Natl. Acad. Sci. U.S.A. 97, 2680-2685 https://doi.org/10.1073/pnas.97.6.2680
  24. Erol A. (2005) The role of fat tissue in the cholesterol lowering and the pleiotropic effects of statins--statins activate the generation of metabolically more capable adipocytes. Med. Hypotheses 64, 69-73 https://doi.org/10.1016/j.mehy.2004.06.014
  25. Kawabe, Y., Sato, R., Matsumoto, A., Honda, M., Wada, Y., Yazaki, Y., Endo, A., Takano, T., Itakura, H. and Kodama, T. (1996) Regulation of fatty acid synthase expression by cholesterol in human cultured cells. Biochem. Biophy. Reser. Commu. 219, 515-520 https://doi.org/10.1006/bbrc.1996.0265
  26. Halestrap, A. P. and Denton, R. M. (1973) Insulin and the regulation of adipose tissue acetyl-Coenzyme A carboxylase. Biochem. J. 132, 509-517

Cited by

  1. Korean red ginseng extract prevents APAP-induced hepatotoxicity through metabolic enzyme regulation: The role of ginsenoside Rg3, a protopanaxadiol vol.33, pp.7, 2013, https://doi.org/10.1111/liv.12046
  2. Efficacy and Safety of Panax notoginseng Saponin Therapy for Acute Intracerebral Hemorrhage, Meta-Analysis, and Mini Review of Potential Mechanisms of Action vol.5, 2015, https://doi.org/10.3389/fneur.2014.00274
  3. Protection Against Hypercholesterolemia by Corni Fructus Extract and Its Related Protective Mechanism vol.12, pp.5, 2009, https://doi.org/10.1089/jmf.2009.0037
  4. Effects of Extracts of Unripe Black Raspberry and Red Ginseng on Cholesterol Synthesis vol.45, pp.5, 2013, https://doi.org/10.9721/KJFST.2013.45.5.628
  5. Effect of high hydrostatic pressure extract of fresh ginseng on adipogenesis in 3T3-L1 adipocytes vol.95, pp.12, 2015, https://doi.org/10.1002/jsfa.6961
  6. The antidiabetic effect of ginsenoside Rb2 via activation of AMPK vol.34, pp.7, 2011, https://doi.org/10.1007/s12272-011-0719-6
  7. Steam-Dried Ginseng Berry Fermented with Lactobacillus plantarum Controls the Increase of Blood Glucose and Body Weight in Type 2 Obese Diabeticdb/dbMice vol.60, pp.21, 2012, https://doi.org/10.1021/jf300460g
  8. Ginseng and obesity 2017, https://doi.org/10.1016/j.jgr.2016.12.005
  9. A Distinctive Pattern ofBeauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells vol.30, pp.1, 2016, https://doi.org/10.1002/ptr.5513
  10. Microencapsulation of ginsenosides using polymerised whey protein (PWP) as wall material and its application in probiotic fermented milk vol.52, pp.4, 2017, https://doi.org/10.1111/ijfs.13365
  11. Panax ginseng and Panax quinquefolius : From pharmacology to toxicology vol.107, 2017, https://doi.org/10.1016/j.fct.2017.07.019
  12. Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative damage and bone-resorbing cytokines during osteogenesis vol.66, 2014, https://doi.org/10.1016/j.bone.2014.06.010
  13. Ginseng and obesity: Observations from assorted perspectives vol.23, pp.4, 2014, https://doi.org/10.1007/s10068-014-0137-x
  14. Ginsenoside Rb2 inhibits osteoclast differentiation through nuclear factor-kappaB and signal transducer and activator of transcription protein 3 signaling pathway vol.92, 2017, https://doi.org/10.1016/j.biopha.2017.05.115
  15. Anti-obesity and anti-inflammatory effects of high hydrostatic pressure extracts of ginseng in high-fat diet induced obese rats vol.10, 2014, https://doi.org/10.1016/j.jff.2014.06.007
  16. Ginsenoside-Rb2 Inhibits Dexamethasone-Induced Apoptosis Through Promotion of GPR120 Induction in Bone Marrow-Derived Mesenchymal Stem Cells vol.24, pp.6, 2015, https://doi.org/10.1089/scd.2014.0367
  17. Cholesterol Improvement Effects of Co-treatment with Black Raspberry and Red Ginseng Extracts in Mice Fed a High Cholesterol Diet vol.43, pp.10, 2014, https://doi.org/10.3746/jkfn.2014.43.10.1491
  18. Linking biological activity with herbal constituents by systems biology-based approaches: effects of Panax ginseng in type 2 diabetic Goto-Kakizaki rats vol.7, pp.11, 2011, https://doi.org/10.1039/c1mb05254c
  19. Metabolomics and traditional Chinese medicine vol.61, 2014, https://doi.org/10.1016/j.trac.2014.06.007
  20. Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy vol.297, pp.6, 2009, https://doi.org/10.1152/ajpheart.00208.2009
  21. A Quantified Ginseng (Panax ginseng C.A. Meyer) Extract Influences Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells vol.16, pp.1, 2011, https://doi.org/10.3390/molecules16010477
  22. KP-3-fermented ginseng in mice fed a high fat diet vol.9, pp.11, 2018, https://doi.org/10.1039/C8FO01056K