• Biomolecules & Therapeutics
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• 제3권2호
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• pp.132-135
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• 1995

Several clofibrate congeners (bezafibrate, gemfibrozil and fenofibrate) were investigated the relationship between effects on the aggregation induced by aggregating agents (thrombin, arachidonic acid, ADP and collagen) and arachidonic acid metabolism in rabbit homogenized platelet. In platelet aggregation study, all drugs produced no significant inhibition (data not shown) in arachidonic acid and thrombin. Also platelet aggregation by ADP was not changed in bezafibrate and Inhibited dose dependently in fenofibrate and gemfibrozil. Platelet aggregation by collagen was inhibited dose dependently and significantly (from p<0.5 to p<0.001) by gemfibrozil and fenofibrate at concentrations between 20 and 400 $\mu$M. In arachidonic acid metabolism study, synthesis of thromboxane $B_2$ was not changed in rabbit platelet membranes and that of prostaglandin $E_2$ and $F_{2{\alpha}}$ was slightly increased by all drugs. It was concluded that clofibrate congeners inhibited ADP and collagen induced rabbit platelet aggregation and inhibition of collagen induced aggregation was probably mediated through some mechanism (pathway) other than arachidonic acid metabolism, judging from arachidonic acid metabolites (thromboxane $B_2$, prostaglandin $E_2$and $F_{ 2{\alpha}}$) synthesis in rabbit homogenized Platelet.

• Toxicological Research
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• 제14권3호
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• pp.333-339
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• 1998

Sambutoxin, a newly purified mycotoxin in Koea, caused hemorrhage in the stomach and intestine of rats. To elucidate the mechanism of hemorrhage, effects of sambutoxin on rabbit platelet aggregation were investigated. First of all, the effects of sambutoxin on the platelet aggregation response and ATP release from platelet by various appregating factors were investigated. And then the role of $Ca^{2+}$ on the platelet aggregation was investigated by flow cytometer. Finally, morphological effect of sambutoxin on platelet ultrastructure was examined by transmission electron microscope. Sambutoxin inhibited aggregation induced by ADP, collagen, thrombin, and arachidonic acid and decreased platelet activating factor-induced disaggregation time in a dose dependent manner. Sambutoxin also decreased thrombin and arachidonic acid-induced ATP release, but increased all factors induced $Ca^{2+}$ release. Sambutoxin showed severe ultrastructural changes of platelet such as appearance of disorganization debri of cellular organelle in intercellular space. Our results indicate that sambutoxin inhibitis rabbit platelet aggregation, and it may be party due to the decrease of ATP release. However, it is not clear whether the antiaggregating effect of sambutoxin is related to $Ca^{2+}$ increase.

• 한국식품위생안전성학회지
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• 제19권3호
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• pp.167-170
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• 2004

The present study was undertaken to investigate the effects of Moutan Cortex Radicis extracts and paeonol, a major component, on rabbit platelet aggregation and thromboxane (TX) $A_2$ formation. Moutan Cortex Radicis methanol and butanol layers (100 ${\mu}g/mL$) showed the weak inhibitions, and water layer (100 ${\mu}g/mL$) had no effect on the collagen-induced platelet aggregation. Whereas, hexane and EtOAc layers potently inhibited the collagen (3 ${\mu}g/mL$)-induced platelet aggregation with the $IC_{50}$ values of 10.9${\pm}$1.0 and 31.5${\pm}$0.8 ${\mu}g/mL$, respectively. Paeonol isolated from the hexane-acetone layer specifically inhibited the collagen-induced platelet aggregation with the $IC_{50}$ value of 113.1 ${\pm}$ 0.9 ${\mu}M$, whereas it had little effects on the other agonists such as AA-, thrombin-, A23187- and thapsigargin-induced platelet aggregations. Paeonol also potently inhibited the collagen-induced TXB formation in rabbit platelet in a concentration-dependent manner. These results suggest that paeonol may inhibit rabbit platelet aggregation by interfering with an essential step in collagen-induced platelet activation and $TXA_2$ formation. Paeonol may be a promising candidate for an antiplatelet agent.

• 대한수의학회지
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• 제36권4호
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• pp.887-894
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• 1996

Cyclopiazonic acid(CPA) known as stimulating the release of intracellular calcium, aflatoxin $B_1(AFB_1)$ causing gastrointestinal hemorrhage frequently were used as model toxic mycotoxins in these studies. First of all, the effects of various mycotoxins on the platelet aggregation response were determined. The effects of mycotoxins on the ATP release from platelet by aggregating factors were investigated. The results and conclusions obtained from these studies are : 1) CPA promoted ADP, collagen, thrombin, A.A. and PAF-induced rabbit platelet aggregation. $AFB_1$ inhibited collagen, A.A. and PAF-induced rabbit platelet aggregation only. 2) CPA increased both aggregation and disaggregation time, whereas $AFB_1$ decreased in a dose dependent manner. 3) CPA increased ADP, thrombin, A.A. and PAF-induced ATP release. $AFB_1$ increased A.A.-induced ATP release and decreased PAF-induced release in a dose dependent manner. In conclusion, CPA promoted platelet aggregation by the increase of ATP. Antiaggregating effects of AFB1 may be due to decreases of ATP. These data provide the basis for the future study of roles of ATP release in platelet aggregation.

• Natural Product Sciences
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• 제11권3호
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• pp.131-135
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• 2005

Methanolic extracts of ninety-five medicinal plants were screened for platelet-activating factor (PAF) receptor binding inhibitory activity using rabbit platelet. Alpinia officinarum, Belamcanda chinensis, Leonurus heterophyllus, Pinus densiflora, Polygonatum sibiricum and Sambucus williamsii showed significant inhibitory effects on the platelet-activating factor (PAF) receptor binding.

• Natural Product Sciences
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• 제2권2호
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• pp.86-89
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• 1996

Methanolic extracts of 25 species of Malaysian medicinal plants were screened for platelet-activating factor (PAF) receptor binding activity using rabbit platelet. Extracts of Cinnamomum sintoc, Ixonanthes iconsandra, Paederia foetida, Piper aduncum, Premna integrifolia, Ardisia crispa, and Ardisia elliptica showed significant inhibitory effect on the platelet-activating factor (PAF) receptor binding.

• 약학회지
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• 제39권1호
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• pp.10-13
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• 1995

As a continuation of the previous studies, a third group of thirty five hot aqueous extracts from natural products were screened for platelet activating factor(PAF) receptor binding antagonistic acitivities using rabbit platelet. The results demonstrate that Arctium lappa is potential source of PAF antagonist.

• Clinical and Experimental Reproductive Medicine
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• 제19권1호
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• pp.9-14
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• 1992

Platelet activating factor(PAF) has been reported to play a significant role in ovulation, establishment and maintnance of early pregnancy. The object of this study was to investigate the influence of PAF on progesterone secretion in rabbit by measurement of pheripheral blood concentration of progesterone. PAF had no effect on progesterone secretion and did not induce decidual reaction in nonovulatory rabbit. But 8th day of hCG induced pesudopregnant rabbit, PAF significantly increase progesterone secretion. Progesterone level was significantly increased at 0.5 and 4 hours after treatment with $10^{-8}$ M PAF on days 2, 4, 6, 8 of gestation as compared than those treated with normal saline. When PAF was injected 2 days after coitus, progesterone levels on days 4, 6, 10, 14 of gestation was significantly increased than those with saline injected group. These results suggest that PAF increase progesterone secretion from the hCG-primed ovary and during pregnancy in rabbit.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.69-69
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• 1997

In the screening of tropical medicinal plants using PAE receptor binding assay, the ether extract of Ardisia crispa showed the potent antagonistic activity. Ardisia crispa have been used to heal the scurf, earache, orchitis, fever and diarrhoea, cough and given to the mother after childbirth to ‘wash out dirty blood’ in Malaysia. By means of activity guided isolation, compound AC7-1 was isolated as the potent PAF antagonist. In this study, antiplatelet effects of compound AC7-1 were examined in vitro platelet aggregation assay using the chronolog aggregometer. Compound AC7-1 inhibited PAF-, collagen-, ADP-, thrombin-induced platelet aggregation in human, rabbit and rat platelet rich plasma. In vitro rabbit platelet aggregation, the IC$\_$50/ value of compound AC7-1 was 5 ${\times}$ 10$\^$-6/ M against PAF(5 ${\times}$ 10$\^$-7/M)-induced aggregation. The IC$\_$50/ values of AC7-1 on PAF-induced platelet aggregation increased with increase of the concentration of PAF used. This result suggested the competitive nature of the AC7-1 antagonism. In vitro rat platelet aggregation, the IC$\_$50/ values of AC7-1 on collagen-, ADP-induced platelet aggregation were 4 ${\times}$ 10$\^$-6/ M, 2 ${\times}$ 10$\^$-5/ M, respectively. Also in vitro human platelet aggregation, AC7-1 potently inhibited both the primary phase and secondary phase of thrombin-induced aggregation.

• Archives of Pharmacal Research
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• 제29권5호
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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.