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http://dx.doi.org/10.5142/JGR.2004.28.2.087

The Mechanism of LDL Receptor Up-regulation by Ginsenoside-Rb2 in HepG2 Cultured under Enriched Cholesterol Condition  

Lim, G-Rewo (Department of Biochemistry, College of Medicine, Konkuk University)
Lee, Hyun-Il (Department of Biochemistry, College of Medicine, Konkuk University)
Kim, Eun-Ju (Department of Biochemistry, College of Medicine, Konkuk University)
Ro, Young-Tae (Department of Biochemistry, College of Medicine, Konkuk University)
Noh, Yun-Hee (Department of Biochemistry, College of Medicine, Konkuk University)
Koo, Ja-Hyun (Department of Biochemistry, College of Medicine, Konkuk University)
Publication Information
Journal of Ginseng Research / v.28, no.2, 2004 , pp. 87-93 More about this Journal
Abstract
The effect of ginsenoside-Rb2, one of a major pharmacological component of Panax ginseng C.A. Meyer, on low density lipoprotein (LDL) receptor expression was investigated and compared with hypocholesterolemic drug lovastatin. In HepG2 cell, exogenous cholesterol decreased LDL receptor mRNA expression, but ginsenoside-Rb2 recovered this reduction of LDL receptor mRNA up to normal expression level. Lovastatin also increased LDL receptor mRNA expression as similar as ginsenoside-Rb2 did. The reduction of sterol regulatory element binding protein (SREBP) transcription by exogenous cholesterol was also similarly recovered by ginsenoside-Rb2 and lovastatin addition. Compound K, a metabolite of ginsenoside-Rb2 and -Rb1 by human intestinal bacteria also increased the SREBP mRNA expression in cholesterol-enriched condition. Ginsenoside-Rb2 seems to up-regulate LDL receptor mRNA expression through the induction of de novo SREBP transcription. Therefore, increased expression of SREBP mRNA by ginsenoside-Rb2 elevated the LDL receptor mRNA expression in HepG2 cells, and these inductions possibly drop the plasma cholesterol level in hypercholesterolemia patients, in vivo, as likely in case of lovastatin.
Keywords
Cholesterol; ginsenoside; SREBP; LDL receptor;
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1 Shinomura, I., Shimano, H., Horton, J. D., Goldstein, J. L. and Brown, M. S. : Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J. Clin. Invest. 99, 838-845 (1997)   DOI   ScienceOn
2 Yoon, M., Lee, H., Jeong, S., Kim, J., Nicol, C. J., Nam, K. W., Kim, M., Cho, B. G. and Oh, T. G. : Peroxisome pro-liferator-activated receptor ${\alpha}$ is involved in the regulation of lipid metabolism by ginseng. Br. J. Pharmacol. 138, 1295-1302 (2003)   DOI   ScienceOn
3 조영동 : 인삼성분의 임상적 효능과 생화학적 작용기전. 고려인삼학회지. 25, 19-25 (2001)
4 Joo, C., Kim, D. and Koo, J. : The effect of ginseng saponin on hypercholesterolemia induced by prolonged cholesterol feeding in rabbits. Korean Biochem. J. 13, 51-58 (1980)
5 이용우, 구자현, 주충노 : 저밀도 지방단백질 수용체 생합성에 관한 연구: (I) 저밀도 지방단백질 수용체 생합성 억제완화에 미치는 ginsenoside의 영향. Korean Biochem. J. 20, 362-367 (1987)
6 Scharnagl, H., Schinker, R., Gierens, H., Nauck, M., Wieland, H. and Marz, W. : Effect of atrovastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglyceride in HepG2 cells. Biochemical pharmacology. 62, 1545-1555 (2001)   DOI   ScienceOn
7 주충노, 강인철, 이희봉 : 인삼사포닌(ginsenoside)이 저밀도 지방단백질 수용체 생합성에 미치는 영향. 고려인삼학회지. 12, 104-113 (1988)
8 노연희, 임그리워, 구자현 : 인삼의 총사포닌, ginsenoside-Rb1, ginsenoside-Rb2와 lovastatin에 의한 HepG2 세포의 HMG-CoA reductase 및 LDL 수용체 mRNA 발현 유발 효과의 비교. 고려인삼학회지. 20, 241-247 (1996)
9 Goldstein, J. L. and Brown, M. S. : Progress in understanding the LDL receptor and HMG-CoA reductase, two membrane proteins that regulate the plasma cholesterol. J. Lipid Res. 25, 1450-1461 (1984)
10 Akao, T., Kida, H., Kanako, M., Hattori, M. and Kobashi, K. : Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rbl from Panax ginseng. J. Pharm. Pharmacol. 50, 1155-1160 (1998)   DOI   ScienceOn
11 Chomczynski, P. and Sacchi, N. : Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloro-form extraction. Anal. Biochem. 163, 156-159 (1987)   DOI
12 Shimano, H. : Sterol regulatory element-binding proteins(SREBPs): transcriptional regulators of lipid synthetic genes. Prog. Lipid Res. 40, 439-452 (2001)   DOI   ScienceOn
13 박성출, 노연희, 구자현 : 고콜레스테롤 조건으로 배양한 HepG2 세포의 콜레스테롤 함량변동과 acyl CoA: cholesterol acyltransferase의 활성에 미치는 인삼성분의 영향. 고려인삼학회지. 19, 212-218 (1995)
14 Wang, X., Sato, R., Brown, M. S., Hua, X. and Goldstein, J. L. : SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 77, 53-62 (1994)   DOI   ScienceOn
15 Hua, X., Yokoyama, C., Wu, J., Briggs, M. R., Brown, M. S., Goldstein, J. L. and Wang, X. : SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc. Natl. Acad. Sci. USA 90, 11603-11607 (1993)   DOI
16 Chawla, A., Repa, J. J., Evans, R. M. and Mangelsdorf, D. J. : Nuclear receptors and lipid physiology: opening the X-files. Science. 294, 1866-1870 (2001)   DOI   ScienceOn
17 Yokoyama, C., Wang, X., Briggs, M. R., Admon, A., Wu, J., Hua, X., Goldstein, J. L. and Brown, M. S. : SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 75, 187-197 (1993)   DOI