DOI QR코드

DOI QR Code

Black ginseng extract ameliorates hypercholesterolemia in rats

  • Saba, Evelyn (Laboratory of Veterinary Physiology and Cell Signaling, Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Jeon, Bo Ra (Laboratory of Veterinary Physiology and Cell Signaling, Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Jeong, Da-Hye (Laboratory of Veterinary Physiology and Cell Signaling, Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Lee, Kija (Laboratory of Medical Imaging, Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Goo, Youn-Kyoung (Department of Parasitology and Tropical Medicine, Kyungpook National University School of Medicine) ;
  • Kim, Seung-Hyung (Institute of Traditional Medicine and Bioscience, Daejeon University) ;
  • Sung, Chang-Keun (Daedeok Bio Corporation Research and Development Center) ;
  • Roh, Seong-Soo (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Kim, Sung Dae (Department of Clinical Research, Research Center, Dongnam Institute of Radiological and Medical Sciences) ;
  • Kim, Hyun-Kyoung (Daedeok Bio Corporation Research and Development Center) ;
  • Rhee, Man-Hee (Laboratory of Veterinary Physiology and Cell Signaling, Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2015.06.01
  • Accepted : 2015.07.06
  • Published : 2016.04.15

Abstract

Background: Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Methods: Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. Results: We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

Keywords

References

  1. Gielen S, Landmesser U. The year in cardiology 2013: cardiovascular disease prevention. Eur Heart J 2014;35:307-12. https://doi.org/10.1093/eurheartj/eht551
  2. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mahonen M, Cepaitis Z, Kuulasmaa K, Keil U. Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations. Lancet 2000;355:688-700. https://doi.org/10.1016/S0140-6736(99)11181-4
  3. Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation 2012;126:126-32. https://doi.org/10.1161/CIRCULATIONAHA.111.087213
  4. Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012;36:16-26. https://doi.org/10.5142/jgr.2012.36.1.16
  5. Lee CH, Kim JH. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 2014;38:161-6. https://doi.org/10.1016/j.jgr.2014.03.001
  6. Lee MR, Yun BS, In OH, Sung CK. Comparative study of Korean white, red, and black ginseng extract on cholinesterase inhibitory activity and cholinergic function. J Ginseng Res 2011;35:421-8. https://doi.org/10.5142/jgr.2011.35.4.421
  7. Lee MR, Kim BC, Kim R, Oh HI, Kim HK, Choi KJ, Sung CK. Anti-obesity effects of black ginseng extract in high fat diet-fed mice. J Ginseng Res 2013;37:308-49. https://doi.org/10.5142/jgr.2013.37.308
  8. Lee MR, Yun BS, Sung CK. Comparative study of white and steamed black Panax ginseng, P. quinquefolium, and P. notoginseng on cholinesterase inhibitory and antioxidative activity. J Ginseng Res 2012;36:93-101. https://doi.org/10.5142/jgr.2012.36.1.93
  9. Paigen B, Morrow A, Brandon C, Mitchell D, Holmes P. Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis 1985;57:65-73. https://doi.org/10.1016/0021-9150(85)90138-8
  10. Im EJ, Yayeh T, Park SJ, Kim SH, Goo YK, Hong SB, Son YM, Kim SD, Rhee MH. Antiatherosclerotic effect of Korean red ginseng extract involves regulator of Gprotein signaling 5. Evid Based Complement Alternat Med 2014;2014:985174.
  11. Qi Y, Liu J, Ma C, Wang W, Liu X, Wang M, Lv Q, Sun J, Liu J, Li Y, et al. Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease. J Lipid Res 2013;54:3189-97. https://doi.org/10.1194/jlr.P040360
  12. Parini P, Davis M, Lada AT, Erickson SK, Wright TL, Gustafsson U, Sahlin S, Einarsson C, Eriksson M, Angelin B, et al. ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver. Circulation 2004;110:2017-23. https://doi.org/10.1161/01.CIR.0000143163.76212.0B
  13. Parini P, Jiang ZY, Einarsson C, Eggertsen G, Zhang SD, Rudel LL, Han TQ, Eriksson M. ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences in normolipidemic, non-obese Chinese patients. Atherosclerosis 2009;207:266-71. https://doi.org/10.1016/j.atherosclerosis.2009.04.010
  14. Haines BE, Steussy CN, Stauffacher CV, Wiest O. Molecular modeling of the reaction pathway and hydride transfer reactions of HMG-CoA reductase. Biochemistry 2012;51:7983-95. https://doi.org/10.1021/bi3008593
  15. Singh DK, Banerjee S, Porter TD. Green and black tea extracts inhibit HMGCoA reductase and activate AMP kinase to decrease cholesterol synthesis in hepatoma cells. J Nutr Biochem 2009;20:816-22. https://doi.org/10.1016/j.jnutbio.2008.07.011
  16. Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov 2003;2:517-26. https://doi.org/10.1038/nrd1112
  17. Shimano H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 2001;40:439-52. https://doi.org/10.1016/S0163-7827(01)00010-8
  18. Shimano H, Shimomura I, Hammer RE, Herz J, Goldstein JL, Brown MS, Horton JD. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest 1997;100:2115-24. https://doi.org/10.1172/JCI119746
  19. VanSaun MN, Lee IK, Washington MK, Matrisian L, Gorden DL. High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model. Am J Pathol 2009;175:355-64. https://doi.org/10.2353/ajpath.2009.080703

Cited by

  1. 방선균 A3265 균주에 의한 인삼 잘록병의 방제 vol.44, pp.3, 2016, https://doi.org/10.4489/kjm.2016.44.3.193
  2. Streptomyces sp. A75와 A501 균주의 인삼 잘록병에 대한 방제효과 vol.44, pp.4, 2016, https://doi.org/10.4489/kjm.2016.44.4.330
  3. Hypolipidemic Effect of Moringa oleifera Lam Leaf Powder and its Extract in Diet-Induced Hypercholesterolemic Rats vol.20, pp.8, 2016, https://doi.org/10.1089/jmf.2016.0155
  4. Beneficial effects of Cirsium japonicum var. maackii on menopausal symptoms in ovariectomized rats vol.9, pp.4, 2016, https://doi.org/10.1039/c7fo01258f
  5. Herbal medicine in the treatment of patients with type 2 diabetes mellitus vol.132, pp.1, 2019, https://doi.org/10.1097/cm9.0000000000000006
  6. Fermented Garlic Ameliorates Hypercholesterolemia and Inhibits Platelet Activation vol.2019, pp.None, 2016, https://doi.org/10.1155/2019/3030967
  7. Shuangyu Tiaozhi Granule Attenuates Hypercholesterolemia through the Reduction of Cholesterol Synthesis in Rat Fed a High Cholesterol Diet vol.2019, pp.None, 2016, https://doi.org/10.1155/2019/4805926
  8. Black Ginseng Extract Prevents Neuroinflammation and Enhances Learning Behavior in Mice vol.18, pp.1, 2016, https://doi.org/10.3923/pjn.2019.51.59
  9. Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects vol.24, pp.10, 2016, https://doi.org/10.3390/molecules24101856
  10. Inhibitory Effects of Ginsenoside Ro on the Growth of B16F10 Melanoma via Its Metabolites vol.24, pp.16, 2019, https://doi.org/10.3390/molecules24162985
  11. In vitro and in silico evaluation of stereoselective effect of ginsenoside isomers on platelet P2Y12 receptor vol.64, pp.None, 2016, https://doi.org/10.1016/j.phymed.2019.152899
  12. Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety vol.11, pp.None, 2016, https://doi.org/10.3389/fphar.2020.00422
  13. Ameliorative effects of black ginseng on nonalcoholic fatty liver disease in free fatty acid-induced HepG2 cells and high-fat/high-fructose diet-fed mice vol.44, pp.2, 2016, https://doi.org/10.1016/j.jgr.2019.09.004
  14. Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions vol.44, pp.4, 2016, https://doi.org/10.1016/j.jgr.2020.03.001
  15. Anti-hyperglycemic and hypolipidemic effects of black ginseng extract containing increased Rh4, Rg5, and Rk1 content in muscle and liver of type 2 diabetic db/db mice vol.29, pp.8, 2020, https://doi.org/10.1007/s10068-020-00753-3
  16. Effect of Korean Red Ginseng on Cholesterol Metabolites in Postmenopausal Women with Hypercholesterolemia: A Pilot Randomized Controlled Trial vol.12, pp.11, 2016, https://doi.org/10.3390/nu12113423
  17. Metabolic Changes in Serum Metabolome of Beagle Dogs Fed Black Ginseng vol.10, pp.12, 2016, https://doi.org/10.3390/metabo10120517
  18. The effect of ginsenoside Rg5, isolated from black ginseng, on heart failure in zebrafish based on untargeted metabolomics vol.76, pp.None, 2016, https://doi.org/10.1016/j.jff.2020.104325
  19. Natural Extracts That Stimulate Adipocyte Browning and Their Underlying Mechanisms vol.10, pp.2, 2021, https://doi.org/10.3390/antiox10020308
  20. Synergistic effects of black ginseng and aged garlic extracts for the amelioration of nonalcoholic fatty liver disease (NAFLD) in mice vol.9, pp.6, 2016, https://doi.org/10.1002/fsn3.2267
  21. The effects of ginseng on the metabolic syndrome: An updated review vol.9, pp.9, 2021, https://doi.org/10.1002/fsn3.2475