| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 88 === Psoralea corylifolia, the dried fruits of Psoralea corylifolia L. (Leguminosae) are used to treat premature ejaculation, spermatorrhea, enuresis, backache, knee pain, and pollakiuria. Externally, it is used for vitiligo, callus, psoriasis, and alopecia. In the previous studies, neobavaisoflavone was purified from the fruits of P. corylifolia and found to inhibit rabbit platelet aggregation and ATP release induced by platelet-activating factor (PAF), arachidonic acid (AA), and U46619 (analog of thromboxane A2). However, its action mechanism has not yet studied in detail. Therefore, this study synthesized 4 and other 5 related compounds (1, 8, 11, 6, 14) to study their effects on PAF-induced rabbit platelet aggregation and the possible underlying action mechanism. In addition, this study also examined their antioxidant activities because flavonoids was reported to have this activity. In PAF-induced aggregation, these compounds (except 1) had inhibitory effect and 4 was the most potent one (IC50 = 17.9 microM). The antiaggregation mechanism of 4 was not due to an inhibition on the PAF receptor but was contributed to the increase of cellular c-AMP and c-GMP and the inhibition on PAF-induced increase of [Ca2+]i. In AA-induced aggregation, these compounds all had inhibitory effect and 4, 11, and 14 were the most potent (IC50 ~ 30 microM). In addition to the action mechanisms mentioned above, an inhibition of thromboxane A2 synthesis and action was also involved. Compound 11 probably was a cyclo-oxygenase inhibitor whereas 4 and 14 probably were thromboxane synthase inhibitors. In antioxidant assay, all 6 compounds scavenged free radical ABTS˙+, indicating having antioxidant activity. Finally, the structure and activity relationships of these 6 compounds were discussed.
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