Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood

Evidence-Based Complementary and Alternative Medicine, Aug 2015

Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as a collagen-induced pressure rate (%) or a collagen concentration required for 50% increase in the pressure rate (PATI value). KBG suppressed the collagen-induced whole blood pressure rate increase and increased the PATI value, like TSS and KSS. Neither RKT nor SKT showed these effects. The Moutan cortex and Cinnamomi cortex, the constituent crude drugs of KBG, showed KBG-like pressure rate suppression and PATI-increasing effects. Furthermore, paeonol, a representative component of Moutan cortex, and aspirin which is known to have platelet aggregation-inhibiting activity (COX-1 inhibitor) also showed similar effects. These results suggest that the platelet aggregation-inhibiting activity of the constituent crude drugs Moutan cortex and Cinnamomi cortex is involved in the improving effects of KBG on impaired microcirculation and that paeonol plays a role in these effects.

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Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood

Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood Kiyoshi Terawaki, Masamichi Noguchi, Mitsutoshi Yuzurihara, Yuji Omiya, Yasushi Ikarashi, and Yoshio Kase Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan Received 31 May 2015; Revised 2 August 2015; Accepted 11 August 2015 Academic Editor: Ching-Liang Hsieh Copyright © 2015 Kiyoshi Terawaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as a collagen-induced pressure rate (%) or a collagen concentration required for 50% increase in the pressure rate (PATI value). KBG suppressed the collagen-induced whole blood pressure rate increase and increased the PATI value, like TSS and KSS. Neither RKT nor SKT showed these effects. The Moutan cortex and Cinnamomi cortex, the constituent crude drugs of KBG, showed KBG-like pressure rate suppression and PATI-increasing effects. Furthermore, paeonol, a representative component of Moutan cortex, and aspirin which is known to have platelet aggregation-inhibiting activity (COX-1 inhibitor) also showed similar effects. These results suggest that the platelet aggregation-inhibiting activity of the constituent crude drugs Moutan cortex and Cinnamomi cortex is involved in the improving effects of KBG on impaired microcirculation and that paeonol plays a role in these effects. 1. Introduction The microcirculatory system is a type of vascular bed including arterioles and capillaries and accounts for more than 90% of the systemic vascular system. Its impairment is related not only to cardiovascular disorders but also to vascular complications of diabetes, hepatic and renal dysfunction, and obstetric and gynecologic conditions such as the oversensitivity to cold. In microcirculatory disturbances, endothelial cells of the vascular wall are damaged, and leukocytes or platelets agglutinate on endothelial cells to form a clot. In addition, the disturbances are also caused by various factors such as increased blood viscosity, active oxygen species, decreased erythrocyte deformability, coagulation/fibrinolysis system, and adhesion factors. In Kampo medicine (traditional Japanese medicine), these complex microcirculatory disturbances are referred to as oketsu (impaired microcirculation) [1, 2]. Keishibukuryogan (KBG), tokishakuyakusan (TSS), and kamisyoyosan (KSS) have been used as oketsu-improving drugs (antioketsu drugs), with KBG particularly showing potent improving effects [3, 4]. It has been suggested that platelet aggregation-inhibiting activity is involved in the improving effects of TSS and KSS on microcirculatory disturbances [5]. However, the effects of KBG on platelet aggregation have been little investigated [6], although increased blood viscosity and reduced erythrocyte deformability are reported to be involved in the antioketsu effects [3, 7]. While platelet-rich plasma (PRP) has been used in platelet aggregation tests [8], PRP has been shown to have effects on the platelet activation and the sensitivity to coagulation stimuli because it is adjusted by centrifugation used in its preparation from whole blood. For this reason, attempts are being made to directly test platelet aggregation using whole blood [9–12]. Moreover, platelet aggregation measured with guinea pig or mouse whole blood has been shown to be similar to that measured with human whole blood [13]. In this study, we used the screen filtration pressure (SFP) method [9–11, 13, 14] with guinea pig whole blood to investigate the mechanistic involvement of platelet aggregation-inhibiting action in the microcirculation disorder-improving effects of KBG and to identify active crude drugs and components contributing to these effects. In addition, TSS and KSS which are known to have platelet aggregation-inhibiting effects [5] and rikkunshito (RKT; a upper gastrointestinal disorder-improving drug) [15–18] and shakuyakukanzoto (SKT; a muscle cramp-improving drug) [19–21], which do not have such effects, were used for comparison to ensure the specificity of KBG. 2. Materials and Methods2.1. Animals Seven-week-old male Hartley guinea pigs weighing 400–500 g were obtained from Japan SLC Inc. (Hamamatsu, Japan). The animals were allowed free access (...truncated)


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Kiyoshi Terawaki, Masamichi Noguchi, Mitsutoshi Yuzurihara, Yuji Omiya, Yasushi Ikarashi, Yoshio Kase. Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood, Evidence-Based Complementary and Alternative Medicine, 2015, 2015, DOI: 10.1155/2015/295706