Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Effect of Korean Red Ginseng on Hypertriglyceridemia in High Fat/high Cholesterol Diet Rat Model

고지방/고콜레스테롤 식이 랫트 모델에서 홍삼에 의한 고중성지방혈증 개선 효과

  • Kim, Hye Yoom (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Jin, Xian Jun (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Hong, Mi Hyeon (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Ko, Seon Mi (Institute of Jinan Red Ginseng) ;
  • Hwang, Seung Mi (Institute of Jinan Red Ginseng) ;
  • Im, Dong joong (Institute of Jinan Red Ginseng) ;
  • Ahn, You Mee (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Lee, Ho Sub (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Kang, Dae Gill (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Lee, Yun Jung (College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University)
  • 김혜윰 (원광대학교 한의과대학 생리학교실) ;
  • 김현준 (원광대학교 한의과대학 생리학교실) ;
  • 홍미현 (원광대학교 한의과대학 생리학교실) ;
  • 고선미 (진안홍삼연구소) ;
  • 황승미 (진안홍삼연구소) ;
  • 임동중 (진안홍삼연구소) ;
  • 안유미 (원광대학교 한의과대학 생리학교실) ;
  • 이호섭 (원광대학교 한의과대학 생리학교실) ;
  • 강대길 (원광대학교 한의과대학 생리학교실) ;
  • 이윤정 (원광대학교 한의과대학 생리학교실)
  • Received : 2017.08.31
  • Accepted : 2017.12.26
  • Published : 2018.02.25
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Abstract

Korean Red Ginseng (RG) are used as a traditional treatment for improve blood circulation. This experimental study was designed to investigate the inhibitory effects of Korean red ginseng on lipid metabolism in high fat/cholesterol diet (HFCD)-induced hypertriglyceridemia. Sprague Dawley rats were fed the HFCD diet with/without fluvastatin (Flu, positive control) 3 mg/kg/day, and RG 125 or 250 mg/kg/day, respectively. All groups received regular diet or HFCD diet, respectively, for 13 weeks. The last three groups treatment of Flu and RG 125, and RG 250 orally for a period of 9 weeks. Group 1, reular diet; group 2, HFCD diet; group 3, Flu + HFCD diet; group 4, RG 125 + HFCD diet; group 5, RG 250 + HFCD diet. As a result, treatment with low or high doses of RG markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. RG and Flu also led to an increase in lipoprotein lipase activity in the HFCD group. On the other hand, RG and Flu led to an decrease in fatty acid synthase and free fatty acid activity in the HFCD group. Treatment with RG suppressed increased expressions of $PPAR-{\alpha}$ and AMPK in HFCD rat liver or muscle. In addition, the RG attenuated triglyceridemia by inhibition of $PPAR-{\gamma}$ and FABP protein expression levels and LXR and SREBP-1 gene expression in liver or muscle. The RG significantly prevented the development of the metabolic disturbances such as hypertriglyceridemia and hyperlipidemia. Taken together, the administration of RG improves hypertriglyceridemia through the alteration in suppression of triglyceride synthesis and accentuated of triglyceride decomposition. These results suggested that RG is useful in the prevention or treatment of hypertriglyceridemia.

Keywords

References

  1. Kreuzer J, Viedt C, Brandes RP, Seeger F, Rosenkranz AS, Sauer H, et al. Platelet-derived growth factor activates production of reactive oxygen species by NAD(P)H oxidase in smooth muscle cells through Gi1, 2. FASEB J. 2003;17:T38-40. https://doi.org/10.1096/fj.01-1036fje
  2. Krauss RM. Triglycerides and atherogenic lipoproteins: rationale for lipid management. Am J Med. 1998;105:58S-62S. https://doi.org/10.1016/S0002-9343(98)00213-7
  3. Janes PJ, Leith CA, Pederson RA. Meal-frequency effects on plasma hormone concentrations and cholesterol synthesis in human. Am J Clin Nutr. 1993;57:868-74. https://doi.org/10.1093/ajcn/57.6.868
  4. Korea National Statistical Office. Annual report on the cause of death statistics. General statistics. Korean Statistical Information Service, Seoul, J Korean Med Assoc. 2016;59(3):221-32 https://doi.org/10.5124/jkma.2016.59.3.221
  5. Michael S. Brown, Joseph L. Goldstein. Disorders of intermediary metabolism. In: Isselbach, Brownwald, Wilson et al. editors. Harrison's Principles Of Internal Medicine. 13th ed. New York: McGraw-Hill. 1994. 2058 p.
  6. Watts GF, Lewis B, Brunt TNH, Lewis S, Coltart DJ, Smith DR, Mann JI, Swan AV. Effects on coronary artery disease of lipid lowering diet of diet plus cholestyramine. in the St. Thomas, atherosclerosis regression study (STARS). Lancet 1992;339:563-9. https://doi.org/10.1016/0140-6736(92)90863-X
  7. Shin MK, Han SH. Effect of lotus leaf powder on lipid concentration in rats fed high fat diet rats. Korean J. Food Culture 2006;21:202-8.
  8. Myung-A Kim. Triglyceride and Cardiovascular Disease. J Lipid Atheroscler. 2013;2(1):1-8. https://doi.org/10.12997/jla.2013.2.1.1
  9. Golan M, Fainaru M, Weizman A. Role of behavior modification in the treatment of childhood obesity with the parents as the exclusive agent of change. Int. J. Obesity 1998;22:1217-24. https://doi.org/10.1038/sj.ijo.0800749
  10. Grundy SM. Hypertriglyceridemia. Atherogenic dyslipidemia, and the metabolic syndrome. Am J Cardiol 1998;81(4A):18B-25B. https://doi.org/10.1016/S0002-9149(98)00033-2
  11. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglyceride to incidence of atherosclerotic coronary artery disease(the PROCAM experience). Prospective Cardiovascular Munster study. Am J Cardiol 1992;70(7):733-7. https://doi.org/10.1016/0002-9149(92)90550-I
  12. Jang SK, Kim JH, Chung YS, Ahn DC, Kang MJ, Lee DG,Kim SH. An Experimental Study on the Effect ofImmunopotential and the Anticancer Effect of Red Ginseng Extract. J Ginseng Res 1994;18:151-9.
  13. Cho JY, Kim AR, Yoo ES, Baik KU, Park MH. Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation. Planta Med. 2002;68:497-500. https://doi.org/10.1055/s-2002-32556
  14. Lee EJ, Ko E, Lee J, Rho S, Ko S, Shin MK, et al. Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation. Int Immunopharmacol. 2004;4:235-44. https://doi.org/10.1016/j.intimp.2003.12.007
  15. An YE, Cho JG, Baik NI, Choi SW, Hur NY, Park SJ, et al. Isolation of 20(S)-Ginsenoside Rg3 and Rg5 from the puffed red ginseng. Food Enginerring progress. 2010;14(2):159-65.
  16. Choi KS, Song H, Kim EH, Choi JH, Hong H, Han YM, et al. Inhibition of hydrogen sulfide-induced angiogenesis and inflammation in vascular endothelial cells: potential mechanisms of gastric cancer prevention by Korean red ginseng. Ginseng Res. 2012;36:135-45. https://doi.org/10.5142/jgr.2012.36.2.135
  17. Park HM, Kim SJ, Go HK, Kim GB, Kim SZ, Kim JS, et al.Korean red ginseng prevents ethanol-induced hepatotoxicity in isolated perfused rat liver. Korean J. Vet. Res. 2011;51:159-64.
  18. Park HM, Kim SJ, Mun AR, Go HK, Kim GB, Kim SZ, et al. Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells. J. Ethnopharmacol. 2012;141:1071-6. https://doi.org/10.1016/j.jep.2012.03.038
  19. Bae EA, Han MJ, Shin YW, Kim DH. Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Biol. Pharm. Bull. 23006;29:1862-7. https://doi.org/10.1248/bpb.29.1862
  20. Choi WY, Lee CG, Seo YC, Song CH, Lim HW, Lee HY. Effect of high pressure and steaming extraction processes on ginsenosides Rg3 and Rh2 contents of cultured-root in wild ginseng (Panax ginseng C. A. Meyer). Korean J. Med. Crop Sci. 2012;20:270-6. https://doi.org/10.7783/KJMCS.2012.20.4.270
  21. Tokumoto T, Tanabe K, Ishida H, Shimmura H, Ishikawa N, Goya N, Akiba T, Toma H. Impact of fluvastatin on hyperlipidemia after renal transplantation.Transplant Proc. 2004;36(7):2141-4. https://doi.org/10.1016/j.transproceed.2004.06.027
  22. Jorge PA, Almeida EA, Ozaki MR, Jorge M, Carneiro A. Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits. Arq Bras Cardiol. 2005;84(4):314-9. https://doi.org/10.1590/S0066-782X2005000400008
  23. Park SH, Jang MJ, Hong JH, Rhee SJ, Choi KH, Park MR. Effects of mulberry leaf extract feeding on lipid status of rats fed high cholesterol diets. J Korean Soc Food Sci Nutr. 2007;36:43-50. https://doi.org/10.3746/jkfn.2007.36.1.043
  24. Rade N. Pejic, MD, and Daniel T. Lee, MD. Hypertriglyceridemia. JABFM. 2006;19(3).
  25. Krauss RM. Triglycerides and atherogenic lipoproteins: rationale for lipid management. Am J Med. 1998;105:58S-62S. https://doi.org/10.1016/S0002-9343(98)00213-7
  26. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F.SREBP transcription factors: master regulators of lipid homeostasis.Biochimie. 2004;86(11):839-48. https://doi.org/10.1016/j.biochi.2004.09.018
  27. Zhang Y, Breevoort SR, Angdisen J, Fu M, Schmidt DR, Holmstrom SR, Kliewer SA, Mangelsdorf DJ, Schulman IG.Liver $LXR{\alpha}$ expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice.J Clin Invest. 2012;122(5):1688-99. https://doi.org/10.1172/JCI59817
  28. Wang G, Bonkovsky HL, de Lemos A, Burczynski FJ. Recent insights into the biological functions of liver fatty acid binding protein 1. J Lipid Res. 2015;56(12):2238-47. https://doi.org/10.1194/jlr.R056705
  29. Newberry EP, Xie Y, Kennedy SM, Luo J, Davidson NO. Protection against Western diet-induced obesity and hepatic steatosis in liver fatty acid-binding protein knockout mice. Hepatology. 2006;44(5):1191-205. https://doi.org/10.1002/hep.21369
  30. Edvardsson U, Ljungberg A, Linden D, William-Olsson L, Peilot-Sjogren H, Ahnmark A, Oscarsson J. PPARalpha activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes.J Lipid Res. 2006;47(2):329-40. https://doi.org/10.1194/jlr.M500203-JLR200
  31. Nevin DN, Brunzell JD, Deeb SS. The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity. Arterioscler Thromb. 1994;14(6):869-73. https://doi.org/10.1161/01.ATV.14.6.869
  32. Wung SF, Kulkarni MV, Pullinger CR, Malloy MJ, Kane JP, Aouizerat BE.The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion. Lipids Health Dis. 2006;5:19. https://doi.org/10.1186/1476-511X-5-19
  33. Sozio MS, Lu C, Zeng Y, Liangpunsakul S, Crabb DW. Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells. Am J Physiol Gastrointest Liver Physiol. 2011;301(4):G739-47. https://doi.org/10.1152/ajpgi.00432.2010
  34. Lee WH, Kim SG. AMPK-Dependent Metabolic Regulation by PPAR Agonists. PPAR Research. 2010;549101:10.
  35. Zhang BB, Zhou G, Li C: AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009;9:407-16. https://doi.org/10.1016/j.cmet.2009.03.012