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Inhibitory effect of disodium quercetin-7,4'-disulfate on aggregation of pig platelets induced by thrombin and its mechanism

  
@article{APS8092,
	author = {Wen Liu and Nian-Ci Liang},
	title = {Inhibitory effect of disodium quercetin-7,4'-disulfate on aggregation of pig platelets induced by thrombin and its mechanism},
	journal = {Acta Pharmacologica Sinica},
	volume = {21},
	number = {8},
	year = {2016},
	keywords = {},
	abstract = {\"AIM:
To study the inhibitory effect of semi-synthesized quercetin derivatives--disodium quercetin-7,4'-disulfate (DQD) on the platelet aggregation induced by thrombin and its mechanism.
METHODS:
Platelet aggregation was analysed by turbidimetry. Cytosolic free calcium concentration ([Ca2+]i) was determined by Fura-2 fluorescence technique. Activity of Ca2+/PL dependent protein kinase C (PKC) was assayed by incubating PKC with histone III S and [gamma-32P]ATP. The cytoskeletal proteins were precipitated by Triton and separated by SDS-PAGE.
RESULTS:
DQD inhibited the platelet aggregation induced by thrombin (500 U/L), when DQD concentrations were 100, 200, and 400 mumol/L, the inhibition rates were 77%, 86%, and 82% respectively. DQD inhibited Ca2+ influx in platelets induced by thrombin (500 U/L) in the presence of extracellular Ca2+ 1 mmol/L in a concentration-dependent manner (10-80 mumol/L); DQD also had inhibitory effect on intracellular Ca2+ mobilization in the absence of extracellular Ca2+. DQD (10-160 mumol/L) inhibited the cytosolic Ca2+/PL dependent PKC from platelets in a concentration-dependent manner, but had no effect on membrane PKC. DQD (20-200 mumol/L) inhibited the actin polymerization induced by thrombin (500 U/L) in platelets in a concentration-dependent manner.
CONCLUSION:
DQD inhibited pig platelet aggregation induced by thrombin and its molecular mechanism was due to its inhibition of Ca2+ influx, intracellular Ca2+ mobilization, Ca2+/PL dependent PKC activity, and actin polymerization.\"},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/8092}
}