| Peer-Reviewed

Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells

Received: 22 January 2014    Accepted: 8 April 2014    Published: 10 April 2014
Views:       Downloads:
Abstract

Little knowledge exists on the lipid-modulating effect of Rubus occidentalis (RO). The present study investigated the molecular mechanisms of lipid-modulating effects of aqueous extract of RO (ROW) in hepatocarcinoma HepG2 cells. ROW decreased apolipoprotein B100 (ApoB100)/apolipoprotein A-1 (ApoA-1) ratio. ROW increased the expression of LDL-receptor (LDL-R). ROW decreased the gene expression of sterol regulatory element-binding protein 1c (SREBP-1c) as well as fatty acid synthase in a concentration-dependent manner. ROW not only down-regulated gene expression of SREBP-2 and HMG-CoA synthase mRNA expression, but also inhibited HMG-CoA reductase activity in a concentration-dependent manner (IC50 = 240.6 μg/ml). These results indicate that ROW decreases the level of bad cholesterol and increases good cholesterol levels by lowering the gene expression of transcription factors, SREBP-1c and SREBP-2, and by inhibiting the expression and/or activity of their downstream enzymes such as fatty acid synthase and HMG-CoA synthase and reductase.

Published in American Journal of BioScience (Volume 2, Issue 2)
DOI 10.11648/j.ajbio.20140202.18
Page(s) 64-69
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Rubus Occidentalis, Apolipoprotein B100, Apolipoprotein A-1, LDL-Receptor, Sterol Regulatory Element-Binding Protein (SREBP), HMG-CoA Reductase

References
[1] Bushakra JM, Stephens MJ, Atmadjaja AN, Lewers KS, Symonds VV, Udall JA, et al. Construction of black (Rubus occidentalis) and red (R. idaeus) raspberry linkage maps and their comparison to the genomes of strawberry, apple, and peach. Theor. Appl. Genet. 2012; 125(2): 311-27.
[2] Seeram NP. Berry fruits: compositional elements, biochemical activities, and the impact of their intake on human health, performance, and disease. J Agric Food Chem. 2008; 56(3): 627-9.
[3] Schreckinger ME, Lotton J, Lila MA, de Mejia EG. Berries from South America: a comprehensive review on chemistry, health potential, and commercialization. J. Med. Food. 2010; 13(2): 233-46.
[4] Prior RL, Wu X, Gu L, Hager T, Hager A, Wilkes S, et al. Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet. Mol. Nutr. Food Res. 2009; 53(11): 1406-18.
[5] Prior RL, Wilkes S, Rogers T, Khanal RC, Wu X, Hager TJ, et al. Dietary black raspberry anthocyanins do not alter development of obesity in mice fed an obesogenic high-fat diet. J. Agric. Food Chem. 2010; 58(7): 3977-83.
[6] Itoh M, Abe Y, Iwama Y, Kimura F, Satoh M, Shoji M, et al. HPLC analysis of lipoproteins in culture medium of hepatoma cells: an in vitro system for screening antihyperlipidemic drugs. Biotechnol. Lett. 2009; 31(7): 953-7.
[7] Schleicher E, Wieland OH. Evaluation of the Bradford method for protein determination in body fluids. J Clin Chem Clin Biochem. 1978; 16(9): 533-4.
[8] Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA. 1979; 76(9): 4350-4.
[9] Scanu AM. Lipoprotein(a) as a cardiovascular risk factor. Trends Cardiovasc. Med. 1991; 1(7): 294-9.
[10] Heneghan HM, Huang H, Kashyap SR, Gornik HL, McCullough AJ, Schauer PR, et al. Reduced cardiovascular risk after bariatric surgery is linked to plasma ceramides, apolipoprotein-B100, and ApoB100/A1 ratio. Surg. Obes. Relat. Dis, 2013; 9: 100-107.
[11] Goldstein JL, Brown MS. The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 2009; 29(4): 431-8.
[12] Jacobson TA. Statin safety: lessons from new drug applications for marketed statins. Am. J. Cardiol. 2006; 97(8A): 44C-51C.
[13] Klopotek A, Hirche F, Eder K. PPAR gamma ligand troglitazone lowers cholesterol synthesis in HepG2 and Caco-2 cells via a reduced concentration of nuclear SREBP-2. Exp. Biol. Med. 2006; 231(8): 1365-72.
[14] Yuan G, Wang J, Hegele RA. Heterozygous familial hypercholesterolemia: an underrecognized cause of early cardiovascular disease. CMAJ. 2006; 174(8): 1124-9.
[15] Vijayakumar MV, Pandey V, Mishra GC, Bhat MK. Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat accumulation and upregulation of LDL receptor. Obesity. 2010; 18(4): 667-74.
[16] Scharnagl H, Marz W. New lipid-lowering agents acting on LDL receptors. Curr. Top. Med. Chem. 2005; 5(3): 233-42.
[17] Kim HJ, Miyazaki M, Man WC, Ntambi JM. Sterol regulatory element-binding proteins (SREBPs) as regulators of lipid metabolism: polyunsaturated fatty acids oppose cholesterol-mediated induction of SREBP-1 maturation. Ann. NY Acad. Sciences. 2002; 967: 34-42.
[18] Yamamoto T, Shimano H, Inoue N, Nakagawa Y, Matsuzaka T, Takahashi A, et al. Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver. J. Biol. Chem. 2007; 282(16): 11687-95.
[19] Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004; 86(11): 839-48.
[20] Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 2002; 109(9): 1125-31.
[21] Jeon TI, Osborne TF. SREBPs: metabolic integrators in physiology and metabolism. Trends Endo. Metanbol. 2012; 23(2): 65-72.
[22] Kajinami K, Mabuchi H, Saito Y. NK-104: a novel synthetic HMG-CoA reductase inhibitor. Expert Opin. Investig. Drugs. 2000; 9(11): 2653-61.
[23] Parker RA, Clark RW, Sit SY, Lanier TL, Grosso RA, Wright JJ. Selective inhibition of cholesterol synthesis in liver versus extrahepatic tissues by HMG-CoA reductase inhibitors. J. Lipid Res. 1990; 31(7): 1271-82.
[24] Gebhardt R. Inhibition of cholesterol biosynthesis by a water-soluble garlic extract in primary cultures of rat hepatocytes. Arzneimittelforschung. 1991; 41(8): 800-4.
[25] Sakakura Y, Shimano H, Sone H, Takahashi A, Inoue N, Toyoshima H, et al. Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis. Biochem. Biophys. Res. Commun. 2001; 286(1): 176-83.
[26] Conde K, Roy S, Freake HC, Newton RS, Fernandez ML. Atorvastatin and simvastatin have distinct effects on hydroxy methylglutaryl-CoA reductase activity and mRNA abundance in the guinea pig. Lipids. 1999; 34(12): 1327-32.
[27] Pal S, Ho N, Santos C, Dubois P, Mamo J, Croft K, et al. Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells. J. Nutr. 2003; 133(3): 700-6.
[28] Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986; 232(4746): 34-47.
Cite This Article
  • APA Style

    Young-Sook Moon, Ju-Hee Han, Tae-Bum Lee, Ji-Wung Kwon, Cheol-Hee Choi. (2014). Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells. American Journal of BioScience, 2(2), 64-69. https://doi.org/10.11648/j.ajbio.20140202.18

    Copy | Download

    ACS Style

    Young-Sook Moon; Ju-Hee Han; Tae-Bum Lee; Ji-Wung Kwon; Cheol-Hee Choi. Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells. Am. J. BioScience 2014, 2(2), 64-69. doi: 10.11648/j.ajbio.20140202.18

    Copy | Download

    AMA Style

    Young-Sook Moon, Ju-Hee Han, Tae-Bum Lee, Ji-Wung Kwon, Cheol-Hee Choi. Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells. Am J BioScience. 2014;2(2):64-69. doi: 10.11648/j.ajbio.20140202.18

    Copy | Download

  • @article{10.11648/j.ajbio.20140202.18,
      author = {Young-Sook Moon and Ju-Hee Han and Tae-Bum Lee and Ji-Wung Kwon and Cheol-Hee Choi},
      title = {Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells},
      journal = {American Journal of BioScience},
      volume = {2},
      number = {2},
      pages = {64-69},
      doi = {10.11648/j.ajbio.20140202.18},
      url = {https://doi.org/10.11648/j.ajbio.20140202.18},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbio.20140202.18},
      abstract = {Little knowledge exists on the lipid-modulating effect of Rubus occidentalis (RO). The present study investigated the molecular mechanisms of lipid-modulating effects of aqueous extract of RO (ROW) in hepatocarcinoma HepG2 cells. ROW decreased apolipoprotein B100 (ApoB100)/apolipoprotein A-1 (ApoA-1) ratio. ROW increased the expression of LDL-receptor (LDL-R). ROW decreased the gene expression of sterol regulatory element-binding protein 1c (SREBP-1c) as well as fatty acid synthase in a concentration-dependent manner. ROW not only down-regulated gene expression of SREBP-2 and HMG-CoA synthase mRNA expression, but also inhibited HMG-CoA reductase activity in a concentration-dependent manner (IC50 = 240.6 μg/ml). These results indicate that ROW decreases the level of bad cholesterol and increases good cholesterol levels by lowering the gene expression of transcription factors, SREBP-1c and SREBP-2, and by inhibiting the expression and/or activity of their downstream enzymes such as fatty acid synthase and HMG-CoA synthase and reductase.},
     year = {2014}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Lipid-Modulating Effects of Aqueous Extract of Rubus Occidentalis in Hepatocarcinoma HepG2 Cells
    AU  - Young-Sook Moon
    AU  - Ju-Hee Han
    AU  - Tae-Bum Lee
    AU  - Ji-Wung Kwon
    AU  - Cheol-Hee Choi
    Y1  - 2014/04/10
    PY  - 2014
    N1  - https://doi.org/10.11648/j.ajbio.20140202.18
    DO  - 10.11648/j.ajbio.20140202.18
    T2  - American Journal of BioScience
    JF  - American Journal of BioScience
    JO  - American Journal of BioScience
    SP  - 64
    EP  - 69
    PB  - Science Publishing Group
    SN  - 2330-0167
    UR  - https://doi.org/10.11648/j.ajbio.20140202.18
    AB  - Little knowledge exists on the lipid-modulating effect of Rubus occidentalis (RO). The present study investigated the molecular mechanisms of lipid-modulating effects of aqueous extract of RO (ROW) in hepatocarcinoma HepG2 cells. ROW decreased apolipoprotein B100 (ApoB100)/apolipoprotein A-1 (ApoA-1) ratio. ROW increased the expression of LDL-receptor (LDL-R). ROW decreased the gene expression of sterol regulatory element-binding protein 1c (SREBP-1c) as well as fatty acid synthase in a concentration-dependent manner. ROW not only down-regulated gene expression of SREBP-2 and HMG-CoA synthase mRNA expression, but also inhibited HMG-CoA reductase activity in a concentration-dependent manner (IC50 = 240.6 μg/ml). These results indicate that ROW decreases the level of bad cholesterol and increases good cholesterol levels by lowering the gene expression of transcription factors, SREBP-1c and SREBP-2, and by inhibiting the expression and/or activity of their downstream enzymes such as fatty acid synthase and HMG-CoA synthase and reductase.
    VL  - 2
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • Department of Pharmacology, Chosun University Medical School, Gwangju 501-759, Republic of Korea

  • Department of Pharmacology, Chosun University Medical School, Gwangju 501-759, Republic of Korea

  • Gochang Black Raspberry Research Institute, Gochang-gun, Jeollabuk-do 585-943, Republic of Korea

  • Gochang Black Raspberry Research Institute, Gochang-gun, Jeollabuk-do 585-943, Republic of Korea

  • Department of Pharmacology, Chosun University Medical School, Gwangju 501-759, Republic of Korea

  • Sections