Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Korean Red Ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells

  • Lee, Seung Eun (Department of Microbiology, School of Medicine, Kyung Hee University) ;
  • Park, Yong Seek (Department of Microbiology, School of Medicine, Kyung Hee University)
  • Received : 2013.06.20
  • Accepted : 2013.09.12
  • Published : 2014.01.15
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Abstract

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other ${\alpha},{\beta}$-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an ${\alpha},{\beta}$-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin Vepropidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

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References

  1. Campbell SC, Moffatt RJ, Stamford BA. Smoking and smoking cessation e the relationship between cardiovascular disease and lipoprotein metabolism: a review. Atherosclerosis 2008;201:225-35. https://doi.org/10.1016/j.atherosclerosis.2008.04.046
  2. Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody JS. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101:10143-8. https://doi.org/10.1073/pnas.0401422101
  3. Gokkusu C, Ademoglu E, Tamer S, Alkan G. Oxidant-antioxidant profiles of platelet rich plasma in smokers. Addict Biol 2001;6:325-30. https://doi.org/10.1080/13556210020077046
  4. Ockene IS, Miller NH. Cigarette smoking, cardiovascular disease, and stroke: a statement for healthcare professionals from the American Heart Association. American Heart Association Task Force on Risk Reduction. Circulation 1997;96:3243-7. https://doi.org/10.1161/01.CIR.96.9.3243
  5. Lee SE, Lee SH, Ryu DS, Park CS, Park KS, Park YS. Differentially-expressed genes related to atherosclerosis in acrolein-stimulated human umbilical vein endothelial cells. Biochip J 2010;4:306-13.
  6. Lee SH, Lee SE, Ahn HJ, Park CS, Cho JJ, Park YS. Identification of atherosclerosis related gene expression profiles by treatment of benzo(a)pyrene in human umbilical vein endothelial cells. Mol Cell Toxicol 2009;5:13-9.
  7. Jeong SI, Lee SE, Yang H, Park CS, Cho JJ, Park YS. MicroRNA microarray analysis of human umbilical vein endothelial cells exposed to benzo(a)pyrene. Biochip J 2012;6:191-6. https://doi.org/10.1007/s13206-012-6212-6
  8. Barnoya J, Glantz SA. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 2005;111:2684-98. https://doi.org/10.1161/CIRCULATIONAHA.104.492215
  9. Aoki M, Nata T, Morishita R, Matsushita H, Nakagami H, Yamamoto K, Yamazaki K, NakabayashiM, Ogihara T, Kaneda Y. Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: antiapoptotic effect of antioxidant agents on endothelial cells. Hypertension 2001;38:48-55. https://doi.org/10.1161/01.HYP.38.1.48
  10. Ouyang JS, Li YP, Li CY, Cai C, Chen CS, Chen SX, Chen YF, Yang L, Xie YP. Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells. Free Radic Res 2012;46:1437-45. https://doi.org/10.3109/10715762.2012.724532
  11. Wu CC, Hsieh CW, Lai PH, Lin JB, Liu YC, Wung BS. Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein. Toxicol Appl Pharmacol 2006;214:244-52. https://doi.org/10.1016/j.taap.2005.12.013
  12. Park BJ, Lim YS, Lee HJ, Eum WS, Park J, Han KH, Choi SY, Lee KS. Antioxidative effects of Phellinus linteus and red ginseng extracts on oxidative stress-induced DNA damage. BMB Rep 2009;42:500-5. https://doi.org/10.5483/BMBRep.2009.42.8.500
  13. Jin YR, Yu JY, Lee JJ, You SH, Chung JH, Noh JY, Im JH, Han XH, Kim TJ, Shin KS, et al. Antithrombotic and antiplatelet activities of Korean red ginseng extract. Basic Clin Pharmacol Toxicol 2007;100:170-5. https://doi.org/10.1111/j.1742-7843.2006.00033.x
  14. Kwak YS, Kyung JS, Kim JS, Cho JY, Rhee MH. Anti-hyperlipidemic effects of red ginseng acidic polysaccharide from Korean red ginseng. Biol Pharm Bull 2010;33:468-72. https://doi.org/10.1248/bpb.33.468
  15. Wong VK, Cheung SS, Li T, Jiang ZH, Wang JR, Dong H, Yi XQ, Zhou H, Liu L. Asian ginseng extract inhibits in vitro and in vivo growth of mouse Lewis lung carcinoma via modulation of ERK-p53 and NF-kappaB signaling. J Cell Biochem 2010;111:899-910. https://doi.org/10.1002/jcb.22778
  16. Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 2000;21:1095-100.
  17. Sung JD, Han KH, Zo JH, Park HJ, Kim CH, Oh BH. Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am J Chin Med 2000;28:205-16. https://doi.org/10.1142/S0192415X00000258
  18. Kim YM, Namkoong S, Yun YG, Hong HD, Lee YC, Ha KS, Lee H, Kwon HJ, Kwon YG, Kim YM. Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-Dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells. Biol Pharm Bull 2007;30:1674-9. https://doi.org/10.1248/bpb.30.1674
  19. Yang H, Lee SE, Jeong SI, Park CS, Jin YH, Park YS. Up-regulation of heme oxygenase-1 by Korean Red Ginseng water extract as a cytoprotective effect in human endothelial cells. J Ginseng Res 2011;35:352-9. https://doi.org/10.5142/jgr.2011.35.3.352
  20. Lee KW, Jung SY, Choi SM, Yang EJ. Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells. BMC Complement Altern Med 2012;12.
  21. Shen T, Lee J, Park MH, Lee YG, Rho HS, Kwak YS, Rhee MH, Park YC, Cho JY. Ginsenoside Rp(1), a ginsenoside derivative, blocks promoter activation of iNOS and COX-2 genes by suppression of an IKK beta-mediated NF-kappa B pathway in HEK293 cells. J Ginseng Res 2011;35:200-8. https://doi.org/10.5142/jgr.2011.35.2.200
  22. Kim YK, Guo Q, Packer L. Free radical scavenging activity of red ginseng aqueous extracts. Toxicology 2002;172:149-56. https://doi.org/10.1016/S0300-483X(01)00585-6
  23. Jeong SI, Lee SE, Yang H, Park CS, Jin YH, Park YS. Effect of alpha,beta-unsaturated aldehydes on endothelial cell growth in bacterial cellulose for vascular tissue engineering. Mol Cell Toxicol 2012;8:119-26. https://doi.org/10.1007/s13273-012-0015-7
  24. Park YS, Kim J, Misonou Y, Takamiya R, Takahashi M, Freeman MR, Taniguchi N. Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase. Arterioscler Thromb Vasc Biol 2007;27:1319-25. https://doi.org/10.1161/ATVBAHA.106.132837
  25. Lee SE, Jeong SI, Kim GD, Yang H, Park CS, Jin YH, Park YS. Upregulation of heme oxygenase-1 as an adaptive mechanism for protection against crotonaldehyde in human umbilical vein endothelial cells. Toxicol Lett 2011;201:240-8. https://doi.org/10.1016/j.toxlet.2011.01.006
  26. Lee SE, Yang H, Jeong SI, Jin YH, Park CS, Park YS. Induction of heme oxygenase- 1 inhibits cell death in crotonaldehyde-stimulated HepG2 cells via the PKC-delta-p38-Nrf2 pathway. PLoS ONE 2012;7.
  27. Jeong SI, Lee SE, Yang H, Park CS, Cho JJ, Park YS. Genome-wide analysis of gene expression by crotonaldehyde in human umbilical vein endothelial cells. Mol Cell Toxicol 2011;7:127-34. https://doi.org/10.1007/s13273-011-0017-x
  28. Lee SE, Park YS. The role of antioxidant enzymes in adaptive responses to environmental toxicants in vascular disease. Mol Cell Toxicol 2013;9: 95-101. https://doi.org/10.1007/s13273-013-0013-4
  29. Park YS, Misonou Y, Fujiwara N, Takahashi M, Miyamoto Y, Koh YH, Suzuki K, Taniguchi N. Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells. Biochem Biophys Res Commun 2005;327:1058-65. https://doi.org/10.1016/j.bbrc.2004.12.104
  30. Lee SE, Park YS. Role of lipid peroxidation-derived a, b-unsaturated aldehydes in vascular dysfunction. Oxid Med Cell Longev 2013;2013:629028. doi: http:// dx.doi.org/10.1155/2013/629028.
  31. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J 1998;12:1063-73. https://doi.org/10.1096/fasebj.12.12.1063
  32. Karaoglu A, Tunc T, Aydemir G, Onguru O, Uysal B, Kul M, Aydinoz S, Oztas E, Sarici U. Role of cyclooxygenase 2 and endothelial nitric oxide synthetase in preclinical atherosclerosis. Fetal Pediatr Pathol 2012;31:432-8. https://doi.org/10.3109/15513815.2012.659408
  33. Burleigh ME, Babaev VR, Oates JA, Harris RC, Gautam S, Riendeau D, Marnett LJ, Morrow JD, Fazio S, Linton MF. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation 2002;105:1816-23. https://doi.org/10.1161/01.CIR.0000014927.74465.7F
  34. Nam KY. The comparative understanding between red ginseng and white ginsengs, processed ginsengs (Panax ginseng C. A. Meyer). J Ginseng Res 2005;29:1-18. https://doi.org/10.5142/JGR.2005.29.1.001
  35. Yang SJ, Woo KS, Yoo JS, Kang TS, Noh YH, Lee JS, Jeong HS. Change of Korean Ginseng components with high temperature and pressure treatment. Korean J Food Sci Technol 2006;38:521-5.
  36. Hien TT, Kim ND, Kim HS, Kang KW. Ginsenoside Rg3 inhibits tumor necrosis factor-alpha-induced expression of cell adhesion molecules in human endothelial cells. Pharmazie 2010;65:699-701.
  37. He F, Guo R, Wu SL, Sun M, Li M. Protective effects of ginsenoside Rb1 on human umbilical vein endothelial cells in vitro. J Cardiovasc Pharmacol 2007;50:314-20. https://doi.org/10.1097/FJC.0b013e3180cab12e
  38. Leung KW, Pon YL, Wong RN, Wong AS. Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells. J Biol Chem 2006;281:36280-8. https://doi.org/10.1074/jbc.M606698200
  39. Kwok HH, Ng WY, Yang MS, Mak NK, Wong RN, Yue PY. The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status. Free Radic Biol Med 2009;48:437-45.
  40. Shin S, Jang JY, Park D, Yon JM, Baek IJ, Hwang BY, Nam SY, Yun YW, Kim KY, Joo SS, et al. Korean red ginseng extract does not cause embryo-fetal death or abnormalities in mice. Birth Defects Res B Dev Reprod Toxicol 2010;89: 78-85.

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