6-ketoprostaglandin-f1-alpha and neferine

Neferine (Nef), a hypotensive agent with antiarrythmic action, is a dibenzyl isoquinoline alkaloid isolated from a Chinese medicinal herb (Nelumbo nucifera Gaertn). Its effects on platelet aggregation and TXA2/PGI2 and cAMP/cGMP balance were studied with methods of turbidimetry and RIA. Nef was shown to significantly inhibit rabbit platelet aggregation induced by ADP, collagen, arachidonic acid (AA) and platelet-activating factor (PAF) with IC50 of 16, 22, 193 and 103 mumol.L-1, respectively. Nef was found to increase vascular 6-keto-PGF1 alpha and platelet cAMP levels in dose-dependent manner, but inhibit AA stimulated TXA2 release from platelets. Nef showed no significant effect on the platelet cGMP level. The results suggest that the mechanism of Nef on platelet aggregation is related to regulation of TXA2/PGI2 and cAMP/cGMP balance.

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Aorta, Thoracic; Benzylisoquinolines; Blood Platelets; Cyclic AMP; Cyclic GMP; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Thromboxane B2

The effects of neferine (Nef), taurine (Tau) and Nef + Tau on platelet aggregation and generation of thrombosis were investigated in rats. Using turbidimetry Nef and Tau were found to inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin. Both drugs reduced the wet weight of experimental thrombosis. But the drugs showed no obvious effect on fibrinogen content and euglobulin lysis time. Thromboxane A2 (TXA2) production induced by ADP and prostacyclin (PGI2) were studied by enzyme immunoassay in rats. TXA2 generation in platelet rich plasma from rats treated with Nef and Nef + Tau obviously decreased. While the plasma PGI2 was not affected. Nef + Tau iv in 30 min significantly decreased the level of total cholesterin in serum. The results suggest that Nef has inhibitory effect on platelet aggregation and thrombosis formation. The combination of both drugs was found to be more potent than either one alone. The mechanism may be related to its reduction of TXA2 formation.

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Benzylisoquinolines; Blood Platelets; Cholesterol; Drug Synergism; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Taurine; Thrombosis; Thromboxane B2