Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

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

고콜레스테롤 조건하에 배양된 HepG2에서의 ginsenoside-Rb2에 의한 LDL receptor 억제 완화 기전

  • 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)
  • 임그리워 (건국대학교 의과대학 생화학교실) ;
  • 이현일 (건국대학교 의과대학 생화학교실) ;
  • 김은주 (건국대학교 의과대학 생화학교실) ;
  • 노영태 (건국대학교 의과대학 생화학교실) ;
  • 노연희 (건국대학교 의과대학 생화학교실) ;
  • 구자현 (건국대학교 의과대학 생화학교실)
  • Published : 2004.06.01
Download PDF
⟨ Previous Next ⟩

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.

인삼성분 중 ginsenoside-Rb$_2$에 의한 LDL receptor발현 증가의 기전을 HepG$_2$세포에서 관찰하였고 이를 lovastatin과 비교하였다. 콜레스테롤 투여에 의하여 억제된 LDL receptor mRNA발현이 ginsenoside-Rb$_2$에 의하여 다시 증가하였고 이는 lovastatin에 의한 증가 효과보다 뛰어났다. SREBP mRNA의 발현 또한 콜레스테롤 투여에 의하여 억제되나 ginseonside-Rb$_2$에 의하여 발현이 증가하였고 이는 lovastatin에 의한 효과와 비슷하였다. 세포에 투여한 ginsenoside-Rb$_2$의 농도에 비례하여 SREBP-1 mRNA의 발현이 증가하였으며 ginsenoside-Rb$_2$의 대사체인 compound K를 투여한 경우에도 SREBP-1 mRNA가 비슷한 양상으로 혹은 더 많이 발현되었다. 따라서 ginsenoside-Rb$_2$에 의한 LDL receptor의 발현 증가는 SREBP의 발현 증가 때문이라고 설명할 수 있다. 즉 ginsenoside-Rb$_2$에 의한 SREBP 발현 증가는 콜레스테롤 투여에 의하여 억제된 LDL receptor발현을 증가시켜 결과적으로 혈중의 콜레스테롤을 효과적으로 제거하는 것으로 판단된다.

Keywords

References

  1. 조영동 : 인삼성분의 임상적 효능과 생화학적 작용기전. 고려인삼학회지. 25, 19-25 (2001)
  2. 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)
  3. 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)
  4. 주충노, 강인철, 이희봉 : 인삼사포닌(ginsenoside)이 저밀도 지방단백질 수용체 생합성에 미치는 영향. 고려인삼학회지. 12, 104-113 (1988)
  5. 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)
  6. 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)
  7. 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) https://doi.org/10.1016/S0092-8674(05)80095-9
  8. 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) https://doi.org/10.1016/0092-8674(94)90234-8
  9. 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) https://doi.org/10.1016/S0006-2952(01)00790-0
  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) https://doi.org/10.1111/j.2042-7158.1998.tb03327.x
  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) https://doi.org/10.1016/0003-2697(87)90021-2
  12. Shimano, H. : Sterol regulatory element-binding proteins(SREBPs): transcriptional regulators of lipid synthetic genes. Prog. Lipid Res. 40, 439-452 (2001) https://doi.org/10.1016/S0163-7827(01)00010-8
  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. 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) https://doi.org/10.1073/pnas.90.24.11603
  15. 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) https://doi.org/10.1172/JCI119247
  16. 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) https://doi.org/10.1038/sj.bjp.0705169
  17. 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) https://doi.org/10.1126/science.294.5548.1866