Abstract
Radix Salviae miltiorrhiza (RSM, ‘Dansham’ in Korea, ‘Danshen’ in Chinese), the root of Salviae miltiorrhiza Bunge (Labiate) has been used as Chinese fork medicine for the treatment of cardiovascular diseases such as angina pectoris, coronary heart disease, myocardial infarction, and hypertension. In the present study, we evaluated the inhibitory effects of 15, 16-Dihydrotanshinone I, one of the major ingredients of Salvia miltiorrhiza Bunge, on platelet aggregation, with elucidation of its mechanisms of action. 15,16-Dihydrotanshinone I concentration-dependently inhibited collagen-induced aggregation of rabbit washed platelets with IC50 of 8.7±5.6 μM, the potency being about seven-fold greater than EGCG, an active Green tea catechin component (IC50: 56.6±48.7 μM). 15,16-Dihydrotanshinone I significantly inhibited the intracellular calcium ([Ca2+]i) mobilization in a concentration-dependent manner. 15,16-dihdydrotanshinone I also significantly suppressed collagen (50 μg/mL)-induced liberation of [3H]Arachidonic acid from [3H]Arachidonic acid-incorporated rabbit platelet. In addition, 15,16-Dihydrotanshinone I at 50 μM slightly but significantly inhibited collagen-induced production of thromboxane B2. These results indicate that 15,16-Dihydrotanshinone I exert potent anti-platelet activity via suppression of [Ca2+]i mobilization and arachidonic acid liberation.
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Balsinde, J., Winstead, M. V., and Dennis, E. A., Phospholipase A2 regulation of arachidonic acid mobilization. FEBS Lett., 531, 2–6 (2002).
Born, G. V. and Cross, M. J., The aggregation of blood platelets. J. Physiol., 168, 178–195 (1963).
Bos, C. L., Richel, D. J., Ritsema, T., Peppelenbosch, M. P., and Versteeg, H. H., Prostanoids and prostanoid receptors in signal transduction. Int. J. Biochem. Cell. Biol., 36, 1187–1205 (2004).
Clemetson, K. J. and Clemetson, J. M., Platelet receptor signaling. Hematol. J., 5, S159–S163 (2004).
Corti, R., Farkouh, M. E., and Badimon, J. J., The vulnerable plaque and acute coronary syndromes. Am. J. Med., 113, 668–680 (2002).
De La Cruz, J. P., Villalobos, M. A., Escalante, R., Guerrero, A., Arrebola, M. M., and Sanchez de la Cuesta, F., Effects of the selective inhibition of platelet thromboxane synthesis on the platelet-subendothelium interaction. Br. J. Pharmacol., 137, 1082–1088 (2002).
Drayer, A. L., Meima, M. E., Derks, M. W., Tuik, R., and van Haastert, P. J., Mutation of an EF-hand Ca2+-binding motif in phospholipase C of Dictyostelium discoideum: inhibition of activity but no effect on Ca2+-dependence. Biochem. J., 311, 505–510 (1995).
Grüner, S., Prostredna, M., Aktas, B., Moers, A., Schulte, V., Krieg, T., Offermanns, S., Eckes, B., and Nieswandt, B., Antiglycoprotein VI treatment severely compromises hemostasis in mice with reduced α2β1 levels or concomitant aspirin therapy. Circulation 110, 2946–2951 (2004).
Grynkiewicz, G., Poenie, M., and Tsien, R. Y., A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 260, 3440–3450 (1985).
Jackson, S. P., Nesbitt, W. S., and Kulkarni, S., Signaling events underlying thrombus formation. J. Thromb. Haemost., 1, 1602–1612 (2003).
Jin, Y. R., Cho, M. R., Ryu, C. K., Chung, J. H., Yuk, D. Y., Hong, J. T., Lee, K. S., Lee, J. J., Lee, M. Y., Lim, Y., and Yun. Y. P., Antiplatelet activity of J78 (2-Chloro-3-[2′-bromo, 4′-fluro-phenyl]-amino-8-hydroxy-1,4-naphthoquinone), an antithrombotic agent, is mediated by thromboxane (TX) A2 receptor blockage with TXA2 synthase inhibition and suppression of cytosolic Ca2+ mobilization J. Pharmacol. Exp. Ther., 312, 214–219 (2005).
Kim, S. Y., Moon, T. C., Chang, H. W., Son, K. H., Kang, S. S., and Kim, H. P., Effects of tanshinone I isolated form Salvia miltiorrhiza Bunge on arachidonic acid metabolism and in vivo inflammatory responses. Phytother. Res., 16, 616–620 (2002).
Lapetina, E. G., The signal transduction induced by thrombin in human platelets. FEBS Lett., 268, 400–404 (1990).
Lee, K. S., Park, J. W., Jin, Y. R., Jung, I. S., Cho, M. R., Yi, K. Y., Yoo, S. E., Chung, H. J., Yun, Y. P., Park, T. K., and Shin, H. S., Antiplatelet activity of [5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine (KR-32570), a novel sodium/hydrogen exchanger-1 and its mechanism of action. Arch. Pharm. Res., 29, 375–383 (2006).
Lin, H. C., Ding, H. Y., and Chang, W. L., Two New Fatty diterpenoids from Salvia miltiorrhiza. J. Nat. Prod., 64, 648–650 (2001).
Lin, H. C., Ding, H. Y., and Chang, W. L., Two new fatty diterpenoids from Salvia miltiorrhiza. J. Nat. Prod., 64, 648–650 (2001).
Luo, H. W., Wu, B. J., Wu, M. Y., Yong, Z. G., and Jin Y., Isolation and structure of danshenxinkun D. Yao Xue Xue Bao., 20, 542–544 (1985).
Ruggeri, J. M., Platelets in atherothrombosis. Nat. Med., 8, 1227–1234 (2002).
Ruggeri, Z. M., von Willebrand factor, platelets and endothelial cell interactions. J. Thromb. Haemost., 1, 1335–1342 (2003).
Sarratt, K. L., Chen, H., Kahn, M.L., and Hammer, D. A., Platelet receptor glycoprotein VI-mediated adhesion to type I collagen under hydrodynamic flow. Ann. Biomed. Eng., 32, 970–976 (2004).
Sarratt, K. L., Chen, H., Zutter, M. M., Santoro, S. A., Hammer, D. A., and Kahn, M. L., GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood 106, 1268–1277 (2005).
Sung, H. J., Choi, S. M., Yoon, Y., and An, K. S., Tanshinone IIA, an ingredient of Salvia miltiorrhiza Bunge induces apoptosis in human leukemia cell lines through the activation of caspase-3. Exp. Mol. Med., 31, 174–178 (1999).
Yokozawa, T., Chung, H. Y., Lee, T. W., Oura, H., Tanaka, T., Nonaka, G., and Nighioka, I., Effect of magnesium ligthospermate B on urinary excretion of arachidonate metabolites in rats with renal failure. Chem.Pharm. Bull., 37, 2766–2769 (1989).
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Park, JW., Lee, SH., Yang, MK. et al. 15,16-Dihydrotanshinone I, a major component from Salvia miltiorrhiza Bunge (Dansham), inhibits rabbit platelet aggregation by suppressing intracellular calcium mobilization. Arch. Pharm. Res. 31, 47–53 (2008). https://doi.org/10.1007/s12272-008-1119-4
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DOI: https://doi.org/10.1007/s12272-008-1119-4