Skip to main content
SpringerLink
Log in

Nutrigenomic analysis of hypolipidemic effects of Agastache rugosa essential oils in HepG2 cells and C57BL/6 mice

  • Research Article
  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Hypolipidemic effects of Agastache rugosa essential oil (AREO) were investigated. Gas chromatographymass spectrometry (GC-MS) analysis showed that the major compound in AREO is limonene (47%, w/w). AREO (1 mg/mL) markedly reduced low density lipoprotein (LDL) oxidation (−93%). After 3-week feeding of AREO, plasma cholesterol (−28%) and triglyceride levels (−26%) were significantly decreased in C57BL/6J mice. Mouse hepatic transcriptome profiling with oligonucleotide microarray revealed that AREO altered the expression of 2,524 genes. Notably, significant reductions in sterol regulatory element binding factor (SREBF)-1 and SREBF-2 mRNA levels were detected. Protein expression of HMG-CoA reductase, a major target for SREBP-2, was reduced in HepG2 cells (−36%) and in mouse liver (−35 %). AREO also significantly increased mRNA (+40%) and protein (+83%) expression of the LDL receptor in HepG2 cells and mouse liver, respectively. Our findings suggest that AREO may prevent atherosclerosis via the inhibition of LDL oxidation, down-regulation of SREBF-2 and HMG-CoA reductase expression, and up-regulation of LDL receptor expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. J. Am. Med. Assoc. 288: 2569–2578 (2002)

    Article  CAS  Google Scholar 

  2. Ansell BJ, Watson KE, Fogelman AM. An evidence-based assessment of the NCEP Adult Treatment Panel II guidelines. National Cholesterol Education Program. J. Am. Med. Assoc. 282: 2051–2057 (1999)

    Article  CAS  Google Scholar 

  3. Steinberg D. Arterial metabolism of lipoproteins in relation to atherogenesis. Ann. NY Acad. Sci. 598: 125–135 (1990)

    Article  CAS  Google Scholar 

  4. Silverstein RL. Inflammation, atherosclerosis, and arterial thrombosis: Role of the scavenger receptor CD36. Cleve. Clin. J. Med. 76(Suppl 2): S27–S30 (2009)

    Article  Google Scholar 

  5. Best JD, Jenkins AJ. Novel agents for managing dyslipidaemia. Expert Opin. Inv. Drug 10: 1901–1911 (2001)

    Article  CAS  Google Scholar 

  6. Hong JH, Choi JH, Oh SR, Lee HK, Park JH, Lee KY, Kim JJ, Jeong TS, Oh GT. Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression; possible mechanism for antiatherogenic effect of Agastache rugosa. FEBS Lett 495: 142–147 (2001)

    Article  CAS  Google Scholar 

  7. Blaszczyk T, Krzyzanowska J, Lamer-Zarawska E. Screening for antimycotic properties of 56 traditional Chinese drugs. Phytother. Res. 14: 210–212 (2000)

    Article  CAS  Google Scholar 

  8. Shin S. Essential oil compounds from Agastache rugosa as antifungal agents against Trichophyton species. Arch. Pharm. Res. 27: 295–299 (2004)

    Article  CAS  Google Scholar 

  9. Shin S, Kang CA. Antifungal activity of the essential oil of Agastache rugosa Kuntze and its synergism with ketoconazole. Lett. Appl. Microbiol. 36: 111–115 (2003)

    Article  CAS  Google Scholar 

  10. Kim HK, Lee HK, Shin CG, Huh H. HIV integrase inhibitory activity of Agastache rugosa. Arch. Pharm. Res. 22: 520–523 (1999)

    Article  CAS  Google Scholar 

  11. Min BS, Hattori M, Lee HK, Kim YH. Inhibitory constituents against HIV-1 protease from Agastache rugosa. Arch. Pharm. Res. 22: 75–77 (1999)

    Article  CAS  Google Scholar 

  12. Sandoval IV, Carrasco L. Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179. J. Virol. 71: 4679–4693 (1997)

    CAS  Google Scholar 

  13. Lee C, Kim H, Kho Y. Agastinol and agastenol, novel lignans from Agastache rugosa and their evaluation in an apoptosis inhibition assay. J. Nat. Prod. 65: 414–416 (2002)

    Article  CAS  Google Scholar 

  14. Grosskopf I, Baroukh N, Lee SJ, Kamari Y, Harats D, Rubin EM, Pennacchio LA, Cooper AD. Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants. Arterioscl. Throm. Vas. 25: 2573–2579 (2005)

    Article  CAS  Google Scholar 

  15. Lee SJ, Grosskopf I, Choi SY, Cooper AD. Chylomicron remnant uptake in the livers of mice expressing human apolipoproteins E3, E2 (Arg158—>Cys), and E3-Leiden. J. Lipid Res. 45: 2199–2210 (2004)

    Article  CAS  Google Scholar 

  16. Chung MJ, Kang AY, Park SO, Park KW, Jun HJ, Lee SJ. The effect of essential oils of dietary wormwood (Artemisia princeps), with and without added vitamin E, on oxidative stress and some genes involved in cholesterol metabolism. Food Chem. Toxicol. 45: 1400–1409 (2007)

    Article  CAS  Google Scholar 

  17. Schuh J, Novogrodsky A, Haschemeyer RH. Inhibition of lymphocyte mitogenesis by autoxidized low-density lipoprotein. Biochem. Bioph. Res. Co. 84: 763–768 (1978)

    Article  CAS  Google Scholar 

  18. Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM. Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. Atherosclerosis 167: 293–302 (2003)

    Article  CAS  Google Scholar 

  19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254 (1976)

    Article  CAS  Google Scholar 

  20. Ritchie ME, Silver J, Oshlack A, Holmes M, Diyagama D, Holloway A, Smyth GK. A comparison of background correction methods for two-color microarrays. Bioinformatics 23: 2700–2707 (2007)

    Article  CAS  Google Scholar 

  21. Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP. Normalization for cDNA microarray data: A robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 30: e15 (2002)

    Article  Google Scholar 

  22. Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193 (2003)

    Article  CAS  Google Scholar 

  23. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. P. Natl. Acad. Sci. USA 98: 5116–5121 (2001)

    Article  CAS  Google Scholar 

  24. Djordjevic D, Cercaci L, Alamed J, McClements DJ, Decker EA. Chemical and physical stability of protein and gum arabic-stabilized oil-in-water emulsions containing limonene. J. Food Sci. 73: C167–C172 (2008)

    Article  CAS  Google Scholar 

  25. Karlberg AT, Magnusson K, Nilsson U. Influence of an anti-oxidant on the formation of allergenic compounds during auto-oxidation of d-limonene. Ann. Occup. Hyg. 38: 199–207 (1994)

    Article  CAS  Google Scholar 

  26. Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein. J. Biol. Chem. 268: 11811–11816 (1993)

    CAS  Google Scholar 

  27. Shashkin P, Dragulev B, Ley K. Macrophage differentiation to foam cells. Curr. Pharm. Design 11: 3061–3072 (2005)

    Article  CAS  Google Scholar 

  28. Daniels TF, Killinger KM, Michal JJ, Wright RW Jr, Jiang Z. Lipoproteins, cholesterol homeostasis, and cardiac health. Int. J. Biol. Sci. 5: 474–488 (2009)

    CAS  Google Scholar 

  29. Brown MS, Goldstein JL. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. P. Natl. Acad. Sci. USA 96: 11041–11048 (1999)

    Article  CAS  Google Scholar 

  30. Ferdowsian HR, Barnard ND. Effects of plant-based diets on plasma lipids. Am. J. Cardiol. 104: 947–956 (2009)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea

    Hee-Jin Jun, Soung-Jin Houng, Sung-Yun Cho, Jungae Jeun, Jin-Young Kim, Kyung Heon Kim, Kuen Woo Park & Sung-Joon Lee

  2. The Nutraceutical Bio Brain Korea 21 Project Group, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea

    Mi Ja Chung

  3. Laboratory for High Performance Computing and Informatics, University of California, Davis MCB, Davis, CA, 95616, USA

    Kevin Dawson & Raymond L. Rodriguez

  4. Nong Shim Co., Gunpo, Gyeonggi, 435-713, Korea

    Cheong-Tae Kim

Authors
  1. Hee-Jin Jun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mi Ja Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin Dawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raymond L. Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soung-Jin Houng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Yun Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jungae Jeun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jin-Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kyung Heon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kuen Woo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cheong-Tae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sung-Joon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Joon Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jun, HJ., Chung, M.J., Dawson, K. et al. Nutrigenomic analysis of hypolipidemic effects of Agastache rugosa essential oils in HepG2 cells and C57BL/6 mice. Food Sci Biotechnol 19, 219–227 (2010). https://doi.org/10.1007/s10068-010-0030-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-010-0030-1

Keywords

Search

Navigation