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Inflammation

, Volume 37, Issue 6, pp 2164–2173 | Cite as

Orientin Inhibits High Glucose-Induced Vascular Inflammation In Vitro and In Vivo

  • Sae-Kwang Ku
  • Soyoung Kwak
  • Jong-Sup BaeEmail author
Article

Abstract

Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Orientin, a C-glycosyl flavonoid, is known to have anxiolytic and antioxidative activity. In this study, we assessed whether orientin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, the expression of cell adhesion molecules (CAMs), the formation of reactive oxygen species (ROS), and the activation of nuclear factor kappa B (NF-κB). Remarkably, the vascular inflammatory effects of HG were attenuated by pretreatment with orientin. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that orientin may have significant benefits in the treatment of diabetic complications and atherosclerosis.

KEY WORDS

orientin high glucose diabetes mellitus inflammation 

Notes

ACKNOWLEDGMENTS

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP) (Grant No. 2013-067053).

Conflict of Interest

The authors declare no conflicts of interest.

REFERENCES

  1. 1.
    Whiting, D.R., L. Guariguata, C. Weil, and J. Shaw. 2011. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Research and Clinical Practice 94: 311–321.PubMedCrossRefGoogle Scholar
  2. 2.
    Grundy, S.M., I.J. Benjamin, G.L. Burke, et al. 1999. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 100: 1134–1146.PubMedCrossRefGoogle Scholar
  3. 3.
    Thomas, J.E., and J.M. Foody. 2007. The pathophysiology of cardiovascular disease in diabetes mellitus and the future of therapy. Journal of the Cardiometabolic Syndrome 2: 108–113.PubMedCrossRefGoogle Scholar
  4. 4.
    Roglic, G., N. Unwin, P.H. Bennett, et al. 2005. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28: 2130–2135.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubino, F., and M. Gagner. 2002. Potential of surgery for curing type 2 diabetes mellitus. Annals of Surgery 236: 554–559.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Day, C. 1998. Traditional plant treatments for diabetes mellitus: pharmaceutical foods. The British Journal of Nutrition 80: 5–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Li, G.Q., A. Kam, K.H. Wong, et al. 2012. Herbal medicines for the management of diabetes. Advances in Experimental Medicine and Biology 771: 396–413.PubMedGoogle Scholar
  8. 8.
    Kumar, S., and A.K. Pandey. 2013. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal 2013: 162750.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Dietrych-Szostak, D., and W. Oleszek. 1999. Effect of processing on the flavonoid content in buckwheat (Fagopyrum esculentum Moench) grain. Journal of Agricultural and Food Chemistry 47: 4384–4387.PubMedCrossRefGoogle Scholar
  10. 10.
    Soulimani, R., C. Younos, S. Jarmouni, D. Bousta, R. Misslin, and F. Mortier. 1997. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. Journal of Ethnopharmacology 57: 11–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Li, Y.L., S.C. Ma, Y.T. Yang, S.M. Ye, and P.P. But. 2002. Antiviral activities of flavonoids and organic acid from Trollius chinensis Bunge. Journal of Ethnopharmacology 79: 365–368.PubMedCrossRefGoogle Scholar
  12. 12.
    Budzianowski, J., G. Pakulski, and J. Robak. 1991. Studies on antioxidative activity of some C-glycosylflavones. Polish Journal of Pharmacology and Pharmacy 43: 395–401.PubMedGoogle Scholar
  13. 13.
    Lee, W., S.K. Ku, and J.S. Bae. 2013. Emodin-6-O-beta-d-glucoside down-regulates endothelial protein C receptor shedding. Archives of Pharmacal Research 36: 1160–1165.PubMedCrossRefGoogle Scholar
  14. 14.
    Bae, J.S., and A.R. Rezaie. 2013. Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand. BMB Reports 46: 544–549.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Kim, T.H., S.K. Ku, I.C. Lee, and J.S. Bae. 2012. Anti-inflammatory functions of purpurogallin in LPS-activated human endothelial cells. BMB Reports 45: 200–205.PubMedCrossRefGoogle Scholar
  16. 16.
    Bae, J.S., W. Lee, and A.R. Rezaie. 2012. Polyphosphate elicits proinflammatory responses that are counteracted by activated protein C in both cellular and animal models. J Thromb Haemost 10: 1145–1151.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Lee, J.D., J.E. Huh, G. Jeon, et al. 2009. Flavonol-rich RVHxR from Rhus verniciflua stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models. International Immunopharmacology 9: 268–276.PubMedCrossRefGoogle Scholar
  18. 18.
    Bae, J.S., W. Lee, J.O. Nam, J.E. Kim, S.W. Kim, and I.S. Kim. 2014. Transforming growth factor beta-induced protein promotes severe vascular inflammatory responses. American Journal of Respiratory and Critical Care Medicine 189: 779–786.PubMedCrossRefGoogle Scholar
  19. 19.
    Lee, W., S.K. Ku, D. Lee, T. Lee, and J.S. Bae. 2014. Emodin-6-O-beta-d-glucoside inhibits high-glucose-induced vascular inflammation. Inflammation 37: 306–313.PubMedCrossRefGoogle Scholar
  20. 20.
    Mackman, N., K. Brand, and T.S. Edgington. 1991. Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. The Journal of Experimental Medicine 174: 1517–1526.PubMedCrossRefGoogle Scholar
  21. 21.
    Laakso, M. 1999. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 48: 937–942.PubMedCrossRefGoogle Scholar
  22. 22.
    Wardle, E.N. 1994. Vascular permeability in diabetics and implications for therapy. Diabetes Research and Clinical Practice 23: 135–139.PubMedCrossRefGoogle Scholar
  23. 23.
    Hamuro, M., J. Polan, M. Natarajan, and S. Mohan. 2002. High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration. Atherosclerosis 162: 277–287.PubMedCrossRefGoogle Scholar
  24. 24.
    Morigi, M., S. Angioletti, B. Imberti, et al. 1998. Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. The Journal of Clinical Investigation 101: 1905–1915.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Boisvert, W.A. 2004. Modulation of atherogenesis by chemokines. Trends in Cardiovascular Medicine 14: 161–165.PubMedCrossRefGoogle Scholar
  26. 26.
    Dunlop, M. 2000. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney International. Supplement 77: S3–S12.PubMedCrossRefGoogle Scholar
  27. 27.
    Han, H.J., Y.J. Lee, S.H. Park, J.H. Lee, and M. Taub. 2005. High glucose-induced oxidative stress inhibits Na+/glucose cotransporter activity in renal proximal tubule cells. American Journal of Physiology. Renal Physiology 288: F988–F996.PubMedCrossRefGoogle Scholar
  28. 28.
    Rimbach, G., G. Valacchi, R. Canali, and F. Virgili. 2000. Macrophages stimulated with IFN-gamma activate NF-kappa B and induce MCP-1 gene expression in primary human endothelial cells. Molecular Cell Biology Research Communications 3: 238–242.PubMedCrossRefGoogle Scholar
  29. 29.
    Uemura, S., H. Matsushita, W. Li, et al. 2001. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circulation Research 88: 1291–1298.PubMedCrossRefGoogle Scholar
  30. 30.
    Kannel, W.B., and D.L. McGee. 1979. Diabetes and cardiovascular disease. The Framingham study. JAMA 241: 2035–2038.PubMedCrossRefGoogle Scholar
  31. 31.
    Nannipieri, M., L. Rizzo, A. Rapuano, A. Pilo, G. Penno, and R. Navalesi. 1995. Increased transcapillary escape rate of albumin in microalbuminuric type II diabetic patients. Diabetes Care 18: 1–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Tooke, J.E. 1995. Microvascular function in human diabetes. A physiological perspective. Diabetes 44: 721–726.PubMedCrossRefGoogle Scholar
  33. 33.
    Gerrity, R.G. 1981. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. The American Journal of Pathology 103: 181–190.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Esposito, C., G. Fasoli, A.R. Plati, et al. 2001. Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC. Kidney International 59: 1842–1849.PubMedCrossRefGoogle Scholar
  35. 35.
    Lopes-Virella, M.F., and G. Virella. 1992. Immune mechanisms of atherosclerosis in diabetes mellitus. Diabetes 41(Suppl 2): 86–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Bae, J.S. 2012. Role of high mobility group box 1 in inflammatory disease: focus on sepsis. Archives of Pharmacal Research 35: 1511–1523.PubMedCrossRefGoogle Scholar
  37. 37.
    Kado, S., T. Wakatsuki, M. Yamamoto, and N. Nagata. 2001. Expression of intercellular adhesion molecule-1 induced by high glucose concentrations in human aortic endothelial cells. Life Sciences 68: 727–737.PubMedCrossRefGoogle Scholar
  38. 38.
    Hansson, G.K., and P. Libby. 2006. The immune response in atherosclerosis: a double-edged sword. Nature Reviews. Immunology 6: 508–519.PubMedCrossRefGoogle Scholar
  39. 39.
    Inoguchi, T., P. Li, F. Umeda, et al. 2000. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939–1945.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Anatomy and Histology, College of Korean MedicineDaegu Haany UniversityGyeongsanRepublic of Korea
  2. 2.College of Pharmacy, CMRI, Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea

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