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Effect of Dai-Saiko-To (Da-Chai-Hu-Tang) on LDL-Receptor Gene Expression in Human Hepatoma Cell Line (HepG2)

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DOI: 10.4236/ajps.2013.42A058    3,164 Downloads   4,668 Views  

ABSTRACT

We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.

Cite this paper

A. Iizuka, F. Yoshie, S. Amagaya, T. Yasuda, M. Iizuka, H. Yamaguchi, S. Nagumo and K. Kondo, "Effect of Dai-Saiko-To (Da-Chai-Hu-Tang) on LDL-Receptor Gene Expression in Human Hepatoma Cell Line (HepG2)," American Journal of Plant Sciences, Vol. 4 No. 2A, 2013, pp. 454-459. doi: 10.4236/ajps.2013.42A058.

References

[1] Multiple Risk Factor Intervention Trial Research Group, “Multiple Risk Factor Intervention Trial. Risk Factor Changes and Mortality Results,” JAMA, Vol. 248, No. 12, 1989, pp. 1465-1477.
[2] M. A. Denke, “Review of Human Studies Evaluating Individual Dietary Responsiveness in Patients with Hypercholesterolemia,” The American Journal of Clinical Nutrition, Vol. 62, No. 2, 1995, pp. 471S-477S.
[3] Lipid Research Clinics Program, “The Lipid Research Clinics Coronary Primary Prevention Trial Results: II. The Relationship of Reduction in Incidence of Coronary Heart Disease to Cholesterol Lowering,” JAMA, Vol. 251, No. 3, 1984, pp. 365-374. doi:10.1001/jama.1984.03340270043026
[4] M. H. Frick, O. Elo, H. Kauko, O. P. Heinonen, P. Heinsalmi, P. Helo, J. K. Huttunen, P. Kaitaniemi, P. Koskinen, V. Manninen, H. M?enp??, M. M?lk?nen, M. M?ntt?ri, S. Norola, A. Pasternack, J. Pikkarainen, M. Romo, T. A. Sj?blom and E. A. Nikkil?, “Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in MiddleAged Men with Dyslipidemia,” The New England Journal of Medicine, Vol. 317, No. 20, 1987, pp. 1237-1245. doi:10.1056/NEJM198711123172001
[5] C. M. Ballantyne, J. Houri, A. Notarbartolo, L. Melani, L. J. Lipka, R. Suresh, S. Sun, A. P. Le Beaut, P. T. Sager and E. P. Veltri, for the Ezetimibe Study Group, “Effect of Ezetimibe Coadministered with Atorvastatin in 628 Patients with Primary Hypercholesterolemia. A Prospective, Randomized, Double-Blind Trial,” Circulation, Vol. 107, 2003, pp. 2409-2415. doi:10.1161/01.CIR.0000068312.21969.C8
[6] M. Yokoyama, H. Origasa, M. Matsuzaki, Y. Matsuzawa, Y. Saito, Y. Ishikawa, S. Oikawa, J. Sasaki, H. Hishida, H. Itakura, T. Kita, A. Kitabatake, N. Nakaya, T. Sakata, K. Shimada and K. Shirato, for the Japan EPA Lipid Intervention Study (JELIS) Investigators, “Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic Patients (JELIS): A Randomised OpenLabel, Blinded Endpoint Analysis,” Lancet, Vol. 369, No. 9567, 2007, pp. 1090-1098. doi:10.1016/S0140-6736(07)60527-3
[7] S. Yamano, F. Sawai, T. Kagoshima and K. Dohi, “Effects of Dai-Saiko-To on Lipid Metabolism and Common Carotid Hemodynamics in Patients with Hyperlipidemia,” Medical and Pharmaceutical Society for WAKAN-YAKU, Vol. 11, 1994, pp. 38-43.
[8] A. Iizuka, T. O. Iijima, F. Yoshie, B. Makino, S. Amagaya, Y. Komatsu, K. Kondo, A. Matsumoto and H. Itakura, “Inhibitory Effects of Dai-Saiko-To on the Progression of Atherosclerotic Lesions in Kurosawa and Kusanagi-Hypercholesterolemic Rabbits,” Journal of Ethnopharmacology, Vol. 63, No. 3, 1998, pp. 209-218. doi:10.1016/S0378-8741(98)00083-X
[9] F. Yoshie, A. Iizuka, K. Kondo, A. Matsumoto, H. Itakura and Y. Komatsu, “Antiatherosclerotic Effect of DaiSaiko-To in Kurosawa and Kusanagi Hypercholesterolemic Rabbits,” Research Communications in Pharmacology and Toxicology, Vol. 5, 2000, pp. 77-89.
[10] F. Yoshie, A. Iizuka, Y. Komatsu, A. Matsumoto, H. Itakura and K. Kondo, “Antiatherosclerotic Effect of DaiSaiko-To in Kurosawa and Kusanagi Hypercholesterolemic Rabbits,” Pharmacological Research, Vol. 50, No. 1-2, 2004, pp. 223-230. doi:10.1016/j.phrs.2004.02.003
[11] K. Mizuno, N. Nakaya, Y. Ohashi, N. Tajima, T. Kushiro, T. Teramoto, S. Uchiyama, H. Nakamura, and for the MEGA Study Group, “Usefulness of Pravastatin in Primary Prevention of Cardiovascular Events in Women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA study),” Circulation, Vol. 117, No. 4, 2008, pp. 494-502. doi:10.1161/CIRCULATIONAHA.106.671826
[12] J. Shepherd, S. M. Cobbe, I. Ford, C. G. Ishes, A. R. Lorimer, P. W. MacFarlane, J. H. McKillop and C. J. Packard, “Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia,” The New England Journal of Medicine, Vol. 333, No. 20, 1995, pp. 1301-1307. doi:10.1056/NEJM199511163332001
[13] T. Teramoto, T. Matsushita, Y. Horie and T. Watanabe, “Production of Apolipoprotein E-Rich LDL by the Liver. The Effect of Dietary Cholesterol and Some Lipid Lowering Agents,” Annals of the New York Academy of Sciences, Vol. 598, 1990, pp. 301-307. doi:10.1111/j.1749-6632.1990.tb42301.x
[14] H. Nakamura, K. Arakawa, H. Itakura, A. Kitabatake, Y. Goto, T. Toyota, N. Nakaya, S. Nishimoto, M. Muranaka, A. Yamamoto, K. Mizuno and Y. Ohashi, “Primary Prevention of Cardiovascular Disease with Pravastatin in Japan (MEGA Study): A Prospective Randomized Controlled Trial,” Lancet, Vol. 368, No. 9542, 2006, pp. 1155-1163. doi:10.1016/S0140-6736(06)69472-5
[15] R. G. Roberto, P. G. Robert, M. Satishkumar, A. M. Sabina, H. M. Carolyn, B. S. McCabe, P. C. Christopher and B. Eugene, “Baseline Low-Density Lipoprotein Cholesterol Is an Important Predictor of the Benefit of Intensive Lipid-Lowering Therapy. A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection TherapyThrombolysis in Myocardial Infection 22) Analysis,” Journal of the American College of Cardiology, Vol. 52, No. 11, 2008, pp. 914-920.
[16] M. N. Salleh, I. Runnie, P. D. Roach, S. Mohamed and M. Y. Abeywardena, “Inhibition of Low-Density Lipoprotein Oxidation and Up-Regulation of Low-Density Lipoprotein Receptor in HepG2 Cells by Tropical Plant Extracts,” Journal of Agricultural and Food Chemistry, Vol. 50, No. 13, 2002, pp. 3693-3697. doi:10.1021/jf011593f
[17] J. Liu, F. Zhang, C. Li, M. Lin and M. R. Briggs, “Synergistic Activation of Human LDL Receptor Expression by SCAP Ligand and Cytokine Oncostatin M,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 1, 2003, pp. 90-96. doi:10.1161/01.ATV.0000046229.77566.E5
[18] S. Yu-Poth, D. Yin, G. Zhao, P. M. Kris-Etherton and T. D. Etherton, “Conjugated Linoleic Acid Upregulates LDL Receptor Gene Expression in HepG2 Cells,” Journal of Nutrition, Vol. 134, No. 1, 2004, pp. 68-71.
[19] A. Iizuka, F. Yoshie, Y. Komatsu, K. Kondo, A. Matsumoto and H. Itakura, “Effect of Dai-Saiko-To on Serum Lipid Levels and APOLIPOPROTEINB, and –E, and LDLReceptor Gene Expression in the Liver of Hypercholesterolemic Rabbits,” Research Communications in Pharmacology and Toxicology, Vol. 6, 2001, pp. 205-214.
[20] K. Yamamoto, Y. Ogawa, T. Yanagita, F. Morita, N. Fukushima, I. Osaki, T. Mizuta, Y. Setoguchi and T. Sakai, “Pharmacological Effects of Dai-Saiko-To on Lipid Biosynthesis in Cultured Human Hepatocyte HepG2 Cells,” Journal of Ethnopharmacology, Vol. 46, No. 1, 1995, pp. 49-54. doi:10.1016/0378-8741(95)01227-5
[21] M. G. L. Hertog, E. J. M. Feskens, P. C. H. Hollman, M. B. Katan and D. Kromhout, “Dietary Antioxidant Flavonoids and Risk of Coronary Heart Disease: The Zutphen Eldery Study,” Lancet, Vol. 342, No. 8878, 1993, pp. 1007-1011. doi:10.1016/0140-6736(93)92876-U
[22] M. Viana, C. Barbas, B. Bonet, M. V. Bonet, M. Castro, M. V. Fraile and E. Herrera, “In Vitro Effects of a Flavonoid-Rich Extract on LDL Oxidation,” Atherosclerosis, Vol. 123, No. 1, 1996, pp. 83-91. doi:10.1016/0021-9150(95)05763-3
[23] C. Bursill, P. D. Roach, C. D. K. Bottema and S. Pal, “Green Tea Upregulates the Low-Density Lipoprotein Receptor through the Sterol-Regulated Element Binding Protein in HepG2 Liver Cell,” Journal of Agricultural and Food Chemistry, Vol. 49, No. 11, 2001, pp. 5639-5645. doi:10.1021/jf010275d
[24] H. Gylling, M. Hallikainen, O. T. Raitakari, M. Laakso, E. Vartiainen, P. Salo, V. Korpelainen, J. Sundvall and T. A. Miettinen, “Long-Term Consumption of Plant Stanol and Sterol Esters, Vascular Function and Genetic Regulation,” British Journal of Nutrition, Vol. 101, No. 11, 2009, pp. 1688-1695. doi:10.1017/S0007114508116300
[25] M. S. Brown and J. L. Goldstein, “The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor,” Cell, Vol. 89, No. 3, 1997, pp. 331-340. doi:10.1016/S0092-8674(00)80213-5
[26] S. V. Harding, T. C. Rideout and P. J. Jones, “Hepatic Nuclear Sterol Regulatory Binding Element Protein 2 Abundance Is Decreased and That of ABCG5 Increased in Male Hamsters Fed Plant Sterols,” Journal of Nutrition, Vol. 140, No. 7, 2010, pp. 1249-1254. doi:10.3945/jn.109.120311
[27] Y. Kimura, M. Kubo, T. Tani, S. Arichi, H. Ohminami and H. Okuda, “Studies on Scutellariae Radix III. Effects on Lipid Metabolism in Serum, Liver and Fat Cells Of Rats,” Chemical and Pharmaceutical Bulletin, Vol. 29, No. 8, 1981, pp. 2308-2312. doi:10.1248/cpb.29.2308

  
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