| Summary: | 碩士 === 國立陽明大學 === 生物化學研究所 === 93 === Platelet-activating factor (PAF) is an important pro-inflammatory mediator produced by various cells. It possesses potent activity for inducing aggregation and a series of inflammatory responses, and may be involved in serious pathological situations such as thrombosis, myocardial infraction and embolismic stroke. There are a number of herbs which were traditionally used to remove thrombi and promote circulation. However, there have been no reports concerning the pharmacological mechanism. Therefore, it is important to find out the components of essential oils isolated from traditional herbs, which have the activity to prevent the platelet aggregation induced by PAF. In the present study, from approximately 210 kinds of essential oils of herbs we found 25 candidates with the inhibitory effect on platelet aggregation induced by 5 nM PAF. The essential oil from P. cablin showed the excellent inhibitory effect, and the active compound, α-bulnesene, isolated from the oil of P. cablin was identified with GC / MS and NMR. According to the results, it showed that α-bulnesene inhibited platelet aggregation induced by PAF with the IC50 value of 24.47 ± 2.45 μM, and then the cytotoxic effect of α-bulnesene was excluded by LDH activity assay. Furthermore, α-bulnesene competitively inhibited [3H] PAF (0.2 nM) binding to PAF receptors on washed platelets with the IC50 value of 17.62 ± 5.68 μM. Moreover, it also concentration-dependently inhibited the PAF-induced intracellular Ca2+ release with the IC50 of 19.62 ± 1.32 μM. On the other hand, the inhibition of MDA biosynthesis revealed that α-bulnesene could interrupt AA metabolic pathway. The inhibition of TXB2 and PGE2 formation also indicated that α-bulnesene interfered with TXA2 production through inhibiting COX activity. Consequently, the above results indicated that α-bulnesene, the active compound isolated from the essential oil of P. cablin, exerted the inhibitory effect on PAF-induced platelet aggregation by competitively inhibiting PAF binding to PAF receptors, inhibited further intracellular Ca2+ mobilization, and inhibited TXA2 formation by interfering with the AA metabolism.
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