Inhibitory effect of GBH on platelet aggregation through inhibition of intracellular Ca2+ mobilization in activated human platelets.
Geiji-Bokryung-Hwan (GBH) was studied on antiplatelet activity in human platelet suspensions. GBH consists of the 5 herbs Cinnamomi Ramulus, Poria Cocos, Mountan Cortex Radicis, Paeoniae Radix, and Persicae Semen, which have been used in herbal medicine for thousands of years for atherosclerosis. The mechanism involved in the antiplatelet activity of GBH in human platelet suspensions was investigated. GBH inhibited platelet aggregation and Ca2+ mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. GBH had no inhibitory effect on thromboxane B2 (TXB2) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca2+ mobilization is regulated by phospholipase C-2 (PLC-gamma2) activation. We evaluated the effect of GBH on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP3). GBH at concentrations that inhibited platelet aggregation and Ca2+ mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP3 induced by CRP. Similar results were obtained with thrombin-induced platelet activation. GBH inhibited platelet aggregation and Ca2+ mobilization induced by thrombin without affecting the production of IP3. We then evaluated the effect of GBH on the binding of IP3 to its receptor. GBH at high concentrations partially blocked the binding of IP3 to its receptor. Therefore, the results suggested that GBH suppresses Ca2+ mobilization at a step distal to IP3 formation. GBH may provide a good tool for investigating Ca2+ mobilization.
Park
Won-Hwan
WH
Department of Biochemistry, Molecular Biology and Diagnostics, Dongguk University College of Oriental Medicine and National Research Laboratory for Glycobiology, Sukjang-Dong 707, Kyungju City, Kyungbuk 780-714, Korea.
Kim
Han-Kyu
HK
Nam
Kyung-Soo
KS
Shon
Yun-Hee
YH
Jeon
Byung Hun
BH
Moon
Sung-Kwon
SK
Kim
Min-Gon
MG
Kim
Cheorl-Ho
CH
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D029001:Herbal Medicine; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007723:Korea; D010455:Peptides / Q000494:pharmacology; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D010738:Type C Phospholipases / Q000378:metabolism
D002352:Carrier Proteins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C435908:collagen-related peptide; D013929:Thromboxane B2; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium