γ-Oryzanol, known as an antiatherosclerotic and an antihyperlipidemia agent, prevents lipid peroxides from forming and accumulating in the vascular wall.
In this experiment, the effects of γ-Oryzanol and ferulic acid (a metabolite of γ-Oryzanol) on prostaglandin metabolism in the vascular wall and platelet were studied.
1) The effect of ferulic acid on PGI
2 production by cultured aortic endothelial cells was evaluated in the presence of histamine (10
-5 M) or Ca ionophore A23187 (5×10
-6 M) which stimulates PGI
2 synthesis. Ferulic acid significantly enhanced the 6-keto-PGF
1α (a stable metabolite of PGI
2; 6KF) production stimulated by histamine or Ca ionophore A23187 in a dose dependent manner, and maximal enhancement was observed at a ferulic acid dose of 200ng/ml. The mean percent increase in 6KF with 200ng/ml of ferulic acid was almost 66% with either stimulant. However, ferulic acid alone did not affect 6KF production at any dose.
2) The effects of ferulic acid on platelet aggregation and platelet thromboxane B
2 (a stable metabolite of thromboxane A
2; TXB
2) production induced by thrombin (0.03U/ml) were also evaluated using washed platelets from healthy volunteers (n=4). Ferulic acid significantly inhibited the platelet aggregation and the platelet TXB
2 production in a dose dependent manner, and its inhibitory effect reached a plateau at a ferulic acid dose of 200ng/ml.
3) γ-Oryzanol was orally given to healthy volunteers (n=9) at a daily dose of 300mg for 2 weeks. Levels of 6KF and TXB
2 in the plasma and the ADP-induced platelet aggregation rate were measured after 1 and 2 weeks of administration. The ratio of 6KF: TXB
2, which mainly regulates the function of platelets in vivo, was significantly elevated by the 2-week administration, though the individual levels of 6KF and TXB
2 in the plasma were not changed significantly. In addition, the platelet aggregation induced by ADP (4μM) was significantly inhibited by the 2-week administration.
These results indicate that γ-Oryzanol and its metabolites can be effective agents for the prostaglandin metabolism in the vascular wall and platelets in vivo, preventing the development of vascular lesions such as atherosclerosis.
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