ABSTRACT Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in arterial thrombotic conditions. The present study aimed to assess the antithrombotic effect of three Kampo, using well-established in vitro and animal models of thrombosis. Western- highfat diet containing 1% Kampo (Shimotsuto, Juzentaihoto or Unseiin) was administered to C57BL/6 mice for 12 weeks. The effect on thrombus formation by laser irradiation of the carotid artery of mice was assessed. In addition the ex-vivo technique of shear-induced platelet reactivity measurement (haemostatometry) and the in vivo test of endothelial function (flowmediated vasodilation) were also used to assess the mechanism of antithrombotic effect. All three medicines have significantly inhibited arterial thrombus formation in mice. According to our studies, the mechanism of antithrombotic effect is based on the inhibition of shear-induced platelet reac- tivity and stimulation of endothelial function (Unseiin). It is assumed that the common ingredients Japanese Angelica Root, Cnidium Rhizome, Peony Root and Rehmannia Root could be responsible for the observed antithrombotic effect.
Cite this paper
nullIjiri, Y. , Anzai, H. , Gao, W. , Takahashi, K. , Kajiwara, N. , Murakami, M. and Yamamoto, J. (2010) Long-term administration of traditional kampo medicine shimotsuto, juzentaihoto and unseiin inhibits experimental thrombosis in mice. Health, 2, 493-498. doi: 10.4236/health.2010.25073.
 Ijiri, Y., Miura, M., Hashimoto, M., Fukunaga, C., Watanabe, S., Kubota, A., Oiwa, K., Okuda, T. and Yamamoto, J. (2002) A new model to evaluate the diet-induced prothrombotic state, using He-Ne laser-induced thrombogenesis in the carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul & Fibrinolysis, 13(6), 497-504.
 Yamamoto, J., Taka, T., Yamada, K., Ijiri, Y., Murakami, M., Hirata, Y., Naemura, A., Hashimoto, M., Yamashita, T., Oiwa, K., Seki, J., Suganuma, H., Inakuma, T. and Yoshida, T. (2003) Tomatoes have natural anti-thrombotic effects. British Journal of Nutrition, 90(6), 1031- 1038.
 Yamamoto, J., Naemura, A., Ijiri, Y., Ogawa, K., Suzuki, T., Shimada, Y. and Giddings, J.C. (2008) The antithrombotic effects of carrot filtrates in rats and mice. Blood Coagul & Fibrinolysis, 19(8), 785-792.
 Kovacs, I.B., Tigyi-Sebes, A., Trombitas, K. and Gorog, P. (1975) Evans blue: An ideal energy-absorbing material to produce intravascular microinjury by He-Ne gas laser. Microvascular Research, 10, 107-124.
 Taka, T., Yoshio, Y., Seki, J., Giddings, J.C. and Yamamoto, J. (2002) Impaired flow-mediated vasodilation in vivo and reduced shear-induced platelet reactivity in vitro in response to nitric oxide in prothrombotic, stroke-prone spontaneously hypertensive rats. Pathophysiology of Haemostasis & Thrombosis, 32, 184-189.
 Tamura, Y., Naemura, A., Inoue, A., Ijiri, Y., Seki, J., Yada, T., Goto, M., Shinohara, M., Kawashima, S., Giddings, J.C. and Yamamoto, J. (2009) Impaired endothelial function may be due to decreased aortic tetrahydrobiopterin, assessed by a new flow-mediated vasodilation in vivo in hypercholesterolemic/atherogenic mice. Blood Coagul & Fibrinolysis, 20(8), 699-705.
 Ratnatunga, C.P., Edmondson, S.F., Rees, G.M. and Kovacs, I.B. (1992) High-dose aspirin inhibits shear-in- duced platelet reaction involving thrombin generation. Circulation, 85(3), 1077-1082.
 Yamamoto, J., Taka, T., Nakajima, S., Ueda, M., Sugimoto, E., Sasaki, Y., Muraki, T., Seki, J. and Watanabe, S. (1999) A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects. Platelets, 10(2), 178-184.
 Goto, H., Shimada, Y., Sekiya, N., Yang, Q., Kogure, T., Mantani, N., Hikiami, H., Shibahara, N. and Terasawa, K. (2004) Effects of keishi-bukuryo-gan on vascular function and hemorheological factors in spontaneously diabetic (WBN/kob) rats. Phytomedicine, 11(2-3), 188-195.
 Yang, Q., Goto, H., Shimada, Y., Kita, T., Shibahara, N. and Terasawa, K. (2002) Effects of choto-san on hemorheological factors and vascular function in stroke-prone spontaneously hypertensive rats. Phytomedicine, 9, 93-98.
 Moens, A.A., Goovaerts, I., Claeys, M.J. and Vrints, C.J. (2005) Flow-mediated vasodilation: A diagnostic instrument, or an experimental tool? Chest, 127(6), 2254-2263.
 Soga, J., Nishioka, K., Nakamura, S., Umemura, T., Jitsuiki, D., Hidaka, T., Teragawa, H., Takemoto, H., Goto, C., Yoshizumi, M., Chayama, K. and Higashi, Y. (2007) Measurement of flow-mediated vasodilation of the brachial artery: A comparison of measurements in the seated and supine positions. Circulation Journal, 71(5), 736-740.
 Matsuo, S., Matsumoto, T., Takashima, H., Ohira, N., Yamane, T., Yasuda, Y., Tarutani, Y. and Horie, M. (2004) The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: Comparison with those to acetylcholine. Journal of Cardiovascular Pharmacology, 44(2), 164- 170.
 Tarutani, Y., Matsumoto, T., Takashima, H., Yamane, T. and Horie, M. (2005) Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor and fibrinolytic responses induced by bradykinin. Hypertension Research, 28(1), 59-66.
 Anderson, T.J., Uehata, A., Gerhard, M.D., Meredith, I.T., Knab, S., Delagrange, D., Lieberman, E.H., Ganz, P., Creager, M.A., Yeung, A.C. and Selwyn, A.P. (1995) Close relation of endothelial function in the human coronary and peripheral circulations. Journal of the American College of Cardiology, 26(5), 1235-1241.
 Engelke, K.A., Halliwill, J.R., Proctor, D.N., Dietz, N.M. and Joyner, M.J. (1996) Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm. Journal of Applied Physiology, 81(4), 1807-1814.
 Makino, T., Wakushima, H., Okamoto, T., Okukubo, Y., Saito, K. and Kano, Y. (2002) Effects of Kangen-karyu on coagulation system and platelet aggregation in mice. Biological & Pharmaceutical Bulletin, 25(4), 523-525.
 Suzuki, Y., Goto, K., Ishige, A., Komatsu, Y. and Kamei, J. (1998) Effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats. Japanese Journal of Pharmacology, 78(1), 87- 91.
 Nakajima, S., Noguchi, T., Taka, T., Ueda, T., Kaizu, K., Fukamizu, M., Fujita, S., Tabuchi, M. and Yamamoto, J. (2000) A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke. Platelets, 11, 459-466.