Abstract
Pro-inflammatory cytokines induce injury of endothelial cells caused by increases of adhesion molecules, leading to vascular inflammation and the development of atherosclerosis. Recent pharmacological studies have demonstrated that vitexicarpin, a flavonoid isolated from Vitex rotundifolia, has anti-inflammatory, antitumor, and analgesic properties. In this study, we investigated whether vitexicarpin (5–100 nM) prevented the TNF-α-induced vascular inflammation process in human umbilical vein endothelial cells (HUVEC). We found that pretreatment with vitexicarpin decreased TNF-α (10 ng/ml)-induced expression of cell adhesion molecules such as vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin as well as matrix metalloproteinase-2 and -9 expression. Preincubation with vitexicarpin also dose-dependently inhibited TNF-α-induced adhesion of HL-60 monocytic cells. Vitexicarpin significantly decreased TNF-α-induced intracellular reactive oxygen species (ROS) production. Furthermore, vitexicarpin suppressed NF-κB nuclear translocation and transcriptional activity in TNF-α-treated HUVEC. In conclusion, vitexicarpin significantly reduced vascular inflammation, through inhibition of ROS–NF-κB pathway in vascular endothelial cells.
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References
Libby, P. 2002. Inflammation in atherosclerosis. Nature 420: 868–874.
Rao, R.M., L. Yang, G. Garcia-Cardena, and F.W. Luscinskas. 2007. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circulation Research 101: 234–47.
Ross, R. 1999. Atherosclerosis—an inflammatory disease. The New England Journal of Medicine 340: 115–126.
de Winther, M.P., E. Kanters, G. Kraal, and M.H. Hofker. 2005. Nuclear factor kappaB signaling in atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 904–914.
Chandrasekar, B., S. Mummidi, L. Mahimainathan, D.N. Patel, S.R. Bailey, S.Z. Imam, W.C. Greene, and A.J. Valente. 2006. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. The Journal of Biological Chemistry 281: 15099–15109.
Chen, J.W., Y.H. Chen, F.Y. Lin, Y.L. Chen, and S.J. Lin. 2003. Ginkgo biloba extract inhibits tumor necrosis factor-alpha-induced reactive oxygen species generation, transcription factor activation, and cell adhesion molecule expression in human aortic endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology 23: 1559–1566.
Gey, K.F., H.B. Stahelin, and M. Eichholser. 1993. Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: panel prospective study. The Journal of Clinical Investigation 71: 3–6.
Islam, K.N., S. Devaraj, and I. Jialal. 1998. Alpha-tocopherol enrichment of monocytes decrease agonist-induced adhesion to human endothelial cells. Circulation 98: 2255–2261.
Ko, W.G., T.H. Kang, S.J. Lee, Y.C. Kim, and B.H. Lee. 2001. Rotundifuran, a labdane type diterpene from Vitex rotundifolia, induces apoptosis in human myeloid leukaemia cells. Phytotherapy Research 15: 535–537.
Ko, W.G., T.H. Kang, S.J. Lee, Y.C. Kim, and B.H. Lee. 2002. Effects of luteolin on the inhibition of proliferation and induction of apoptosis in human myeloid leukaemia cells. Phytotherapy Research 16: 295–298.
You, K.M., K.H. Son, H.W. Chang, S.S. Kang, and H.P. Kim. 1998. Vitexicarpin, a flavonoid from the fruits of Vitex rotundifolia, inhibits mouse lymphocyte proliferation and growth of cell lines in vitro. Planta Medica 64: 546–550.
Mesaik, M.A., Azizuddin, S. Murad, K.M. Khan, R.B. Tareen, A. Ahmed, Atta-ur-Rahman, and M.I. Choudhary. 2009. Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus. Phytotherapy Research 23: 1516–1520.
Ko, W.G., T.H. Kang, S.J. Lee, N.Y. Kim, Y.C. Kim, D.H. Sohn, and B.H. Lee. 2000. Polymethoxyflavonoids from Vitex rotundifolia inhibit proliferation by inducing apoptosis in human myeloid leukemia cells. Food and Chemical Toxicology 38: 861–865.
Shanafelt, T.D., T.G. Call, C.S. Zent, B. LaPlant, D.A. Bawen, M. Roos, C.R. Secreto, A.K. Ghosh, B.F. Kabat, M.J. Lee, C.S. Yang, D.F. Jelinek, C. Erlichman, and N.E. Kay. 2009. Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia. Journal of Clinical Oncology 27: 3080–14.
Manduteanu, I., M. Voinea, F. Antohe, E. Dragomir, M. Capraru, L. Radulescu, and M. Simionescu. 2003. Effect of enoxaparin on high glucose-induced activation of endothelial cells. European Journal of Pharmacology 477: 269–276.
Dschietzig, T., C. Richter, G. Pfannenschmidt, C. Bartsch, M. Laule, G. Baumann, and K. Stangl. 2001. Dexamethasone inhibits stimulation of pulmonary endothelins by proinflammatory cytokines: possible involvement of a nuclear factor kappa B dependent mechanism. Intensive Care Medicine 27: 751–756.
Choi, Y.S., S. Kim, H.K. Lee, K.U. Lee, and Y.K. Pak. 2004. In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A. Biochemical and Biophysical Research Communications 314: 118–122.
Zhou, M., Z. Diwu, N. Panchuk-Voloshina, and R.P. Haugland. 1997. A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Analytical Biochemistry 253: 162–168.
Iglesias, J., V.E. Abernethy, Z. Wang, W. Lieberthal, J.S. Koh, and J.S. Levine. 1999. Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS. The American Journal of Physiology 277: 711–722.
Lee, Y.J., S.M. Hwang, D.G. Kang, J.S. Kim, and H.S. Lee. 2009. Effect of Gastrodia elata on tumor necrosis factor-alpha-induced matrix metalloproteinase activity in endothelial cells. Journal of Natural Medicines 63: 463–467.
Carlos, T., N. Kovach, B. Schwartz, M. Rosa, B. Newman, E. Wayner, C. Benjamin, L. Osborn, R. Lobb, and J. Harlan. 1991. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood 77: 2266–2271.
Basalyga, D.M., D.T. Simionescu, W. Xiong, B.T. Baxter, B.C. Starcher, and N.R. Vyavahare. 2004. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation 110: 3480–3487.
Toth, M., M.M. Bernardo, D.C. Gervasi, P.D. Soloway, Z. Wang, H.F. Bigg, C.M. Overall, Y.A. DeClerck, H. Tschesche, M.L. Cher, S. Brown, S. Mobashery, and R. Fridman. 2000. Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of pro-MMP-2. The Journal of Biological Chemistry 275: 41415–41423.
Victor, V.M., M. Rocha, E. Solá, C. Bañuls, K. Garcia-Malpartida, and A. Hernández-Mijares. 2009. Oxidative stress, endothelial dysfunction and atherosclerosis. Current Pharmaceutical Design 15: 2988–3002.
Kanters, E., M. Pasparakis, M.J. Gijbels, M.N. Vergouwe, I. Partouns-Hendriks, R.J. Fijneman, B.E. Clausen, I. Förster, M.M. Kockx, K. Rajewsky, G. Kraal, M.H. Hofker, and M.P. de Winther. 2003. Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. The Journal of Clinical Investigation 112: 1176–1185.
Liang, Y., Y. Zhou, and P. Shen. 2004. NF-kappaB and its regulation on the immune system. Cellular and Molecular Immunology 1: 343–350.
Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010–0029465) and a grant [K10040] to Dr. DG Kang funded by Korea Institute of Oriental Medicine.
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Lee, S.M., Lee, Y.J., Kim, Y.C. et al. Vascular Protective Role of Vitexicarpin Isolated from Vitex rotundifolia in Human Umbilical Vein Endothelial Cells. Inflammation 35, 584–593 (2012). https://doi.org/10.1007/s10753-011-9349-x
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DOI: https://doi.org/10.1007/s10753-011-9349-x