Effects of tetrandrine and fangchinoline on human platelet aggregation and thromboxane B2 formation.
Tetrandrine (TET) and fangchinoline (FAN) are two major components of the radix of Stephania tetrandra. The effects of TET and FAN on human platelet aggregation and formation of thromboxane (TX) B2, a stable metabolite of TXA2, were examined in the aspect of platelet aggregation. TET and FAN inhibited platelet-activating factor (PAF)-induced human platelet aggregation. IC50 values for TET and FAN were 28.6+/-3.24 microM and 21.7+/-2.61 microM, respectively. In the PAF-receptor binding assay, neither TET nor FAN showed any inhibitory effects on the specific bindings of PAF to its receptor. TET and FAN also inhibited PAF-, thrombin- and arachidonic acid-induced thromboxane B2 formation in human washed platelet. These results indicate that TET and FAN inhibit the platelet aggregation by interfering with the intracellular messengers system, but not by inhibiting the binding of PAF to PAF-receptor on the platelet membrane directly, and the suppression of TXA2 formation by TET and FAN may be responsible for their inhibitory activities on the platelet aggregation and further on the thrombosis.
Kim
H S
HS
Department of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju, South Korea. hskim@trut.chungbuk.ac.kr
Zhang
Y H
YH
Fang
L H
LH
Yun
Y P
YP
Lee
H K
HK
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D044182:Benzylisoquinolines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013929:Thromboxane B2 / Q000096:biosynthesis*
D000470:Alkaloids; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C009438:tetrandrine; D013929:Thromboxane B2; C060802:fangchinoline