• Archives of Pharmacal Research
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• v.29 no.5
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• The Journal of Dong Guk Oriental Medicine
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• v.2 no.1
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• pp.19-54
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• 1993

To see both $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$(dissipate phlegm and promote vital energy circulation) and $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$(blood circulation and disperse blood stasis) influencing on thrombosis, contusion-hyperemia, and hyperlipidemia, at first we measured the density of FDP, the quantity of fibrinogen, prothrombin time, and the number of platelet of rat taken thrombosis by endotoxin. Secondly we measured the increase-rate of "paw swelling", the number of platelet, the quantity of fibrinogen, and prothrombin time of rat taken contusion-hyperemia. And then we measured the quantity of total cholesterol in serum and of H.D.L-cholesterol and of triglyceride and of phospholipid and of ${\beta}-lipoprotein$, its weight, and the variation of the quantity of electrolyte of rat taken hyperlipidemia by the oral-injection of choleserol. As a result, we can conclude as follows : 1. Out of the test of thrombosis, we can recognize not only the noticeable increae of the number of platelet and the quantity of fibrinogen, but also the noticeable decrease of prothrombin time and the density of FDP in case of $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$-injected rat and $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$-injected rat. 2. Out of the test of contusion-hyperemia, we can recognize not only the noticeable increase of the number of platelet and the quantity of fibrinogen, but also the noticeable decrease of prothrombin time and "increase-rate of paw swelling" in case of $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$-injected rat and $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$-injected rat. 3. Out of the test of hyperlipidemia, at first we can recognize that test rat's weight increased as close as that of normal rat. And we can recognize the noticeable decrease of the triglyceride and phospholipid and ${\beta}-lipoprotein$." Also, in case of the variation of electrolyte we can recognize the decrease of calcium and potassium in $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$-injected rat, and of sodium and magnesium in $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$-injected rat. Thus, as the above-mentioned, in covering thrombosis, contusion-hypermia, and hyperlipidemia, the effect of $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$ and $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$ can be recognized. Granting that $Hu{\grave{a}}y{\bar{u}}t{\bar{a}}ng$ reveals its effectiveness in thrombosis and contusion-hyperemia, and $Sh{\grave{u}}nq{\grave{i}}daot{\acute{a}}nt{\bar{a}}ng$ in hyperlipidemia, it can be inferred that contusion-hyperemia is like "model of blood stasis form" as thrombosis and hyperlipidemia "phlegm-retention diseases form", and both phlegm-retention and blood stasis have correlation each other.