YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effect of Curcuma Longa Derived-curcumin on Vascular Tension

강황 유래 Curcumin의 Rho-kinase 억제를 통한 혈관이완작용

  • Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • 제현동 (대구가톨릭대학교 약학대학 약물학교실)
  • Received : 2013.08.09
  • Accepted : 2013.10.22
  • Published : 2013.10.31
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Abstract

The present study was undertaken to investigate the influence of curcumin on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that curcumin, the primary ingredient of Curcuma longa, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, curcumin inhibited fluoride-induced contraction but didn't inhibit phorbol ester-induced contraction suggesting that additional pathways different from endothelial nitric oxide synthesis might be involved in the vasorelaxation. Furthermore, curcumin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving inhibition of fluoride-induced MYPT1 phosphorylation. This study provides evidence that curcumin induces vascular relaxation through inhibition of Rho-kinase in rat aortae.

Keywords

References

  1. Lydakis, C., Lip, G. Y. H., Beevers, M. and Beevers, D. G. : Diet, lifestyle and blood pressure. Coronary Health Care 1, 130 (1997). https://doi.org/10.1016/S1362-3265(97)80003-X
  2. Singh, M. and Singh, N. : Curcumin counteracts the proliferative effect of estradiol and induces apoptosis in cervical cancer cells. Mol. Cell. Biochem. 347, 1 (2011). https://doi.org/10.1007/s11010-010-0606-3
  3. Li, R., Xiang, C., Ye, M., Li, H. F., Zhang, X. and Guo, D. A. : Qualitative and quantitative analysis of curcuminoids in herbal medicines derived from Curcuma species. Food Chemistry 126, 1890 (2011). https://doi.org/10.1016/j.foodchem.2010.12.014
  4. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  5. Somlyo, A. P. and Somlyo, A. V. : From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand. 164, 437 (1998). https://doi.org/10.1046/j.1365-201X.1998.00454.x
  6. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. : Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990 (1997). https://doi.org/10.1038/40187
  7. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. : $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548 (2003). https://doi.org/10.1161/01.RES.0000090998.08629.60
  8. Kitazawa, T., Masuo, M. and Somlyo, A. P. : Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 88, 9307 (1991). https://doi.org/10.1073/pnas.88.20.9307
  9. Gohla, A., Schultz, G. and Offermanns, S. : Roles for G(12)/ G(13) in agonist-induced vascular smooth muscle cell contraction. Circ. Res. 87, 221 (2000). https://doi.org/10.1161/01.RES.87.3.221
  10. Leung, T., Manser, E., Tan, L. and Lim, L. : A novel serine/ threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem. 270, 29051 (1995). https://doi.org/10.1074/jbc.270.49.29051
  11. Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K. : Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO. J. 15, 2208 (1996).
  12. Wier, W. G. and Morgan, K. G. : Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91 (2003).
  13. Jeon, S. B., Jin, F., Kim, J. I., Kim, S .H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim, I. K. : A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27 (2006). https://doi.org/10.1016/j.bbrc.2006.02.120
  14. Wilson, D. P., Susnjar. M., Kiss, E., Sutherland, C. and Walsh, M. P. : Thromboxane A2-induced contraction of rat caudal arteria lsmooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763 (2005). https://doi.org/10.1042/BJ20050237
  15. Wooldridge, A. A., MacDonald, J. A., Erdodi, F., Ma, C., Borman, M. A., Hartshorne, D. J. and Haystead, T. A. : Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J. Biol. Chem. 279, 34496 (2004). https://doi.org/10.1074/jbc.M405957200
  16. Park, W., Amin, A. R., Chen, Z. G. and Shin, D. M. : New Perspectives of Curcumin in Cancer Prevention. Cancer. Prev. Res. (Phila). 6, 387 (2013). https://doi.org/10.1158/1940-6207.CAPR-12-0410