Effects of d-003, a new substance purified from sugar cane wax, on platelet aggregation and plasma levels of arachidonic acid metabolites in healthy volunteers.
D-003 is a mixture of very high molecular weight aliphatic acids purified from sugar cane wax showing cholesterol-lowering and antiplatelet effects proven in experimental and clinical studies. Experimental evidence indicates that inhibition of platelet aggregation induced by D-003 is associated with a reduction of thromboxane B2 (TxB2) and an increase of prostacyclin (Pgl2) serum levels. This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers. Thirty-one subjects were randomized to placebo or D-003 at 20 mg/day for 14 days. Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed. D-003 (20 mg/day) significantly reduced (p < 0.001) TxB2by 36.4% and increased Pgl2 serum levels by 31% compared with baseline, and these changes were different from placebo. As expected, D-003 significantly inhibited (p < 0.001) platelet aggregation to AA (81.9-65.6%) and to collagen (75.3-62.3%). No subject withdrew from the study. No drug-related disturbances were observed. We conclude that D-003 at 20 mg/day for 14 days significantly inhibited platelet aggregation to AA and collagen and reduced TxB2 and increased Pgl2 serum levels. These results are consistent with those observed in experimental models, indicating that the antiplatelet effect of D-003 is associated with the observed changes on the levels of AA metabolites. Further studies, however, should explore the mechanism involved in this action in greater depth.
Arruzazabala
M L
ML
Center for Natural Products of the National Center for Scientific Research, Havana City, Cuba.
Mas
R
R
Molina
V
V
Carbajal
D
D
Fernández
L
L
Illnait
J
J
Castaño
G
G
Fernández
J
J
Mendoza
S
S
D000328:Adult; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000097:blood*; D001247:Asthenia / Q000139:chemically induced; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000097:blood; D005227:Fatty Acids / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D031786:Saccharum / Q000737:chemistry*; D013607:Tablets; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood; D013997:Time Factors; D014885:Waxes / Q000737:chemistry / Q000302:isolation & purification*
D001095:Arachidonic Acids; D024042:Collagen Type I; C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D010936:Plant Extracts; D013607:Tablets; D014885:Waxes; D013929:Thromboxane B2; D011464:Epoprostenol