Chemical Structure-Activity of Cnidium Rhizome-Derived Phthalides for the Competence Inhibition of Proliferation in Primary Cultures of Mouse Aorta Smooth Muscle Cells

Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6, 7-dihydroligustilide) > senkyunolide H (((Z)-6, 7-dihydroxy-6, 7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6, 7-dihydroxy-3, 6, 7, 8-tetrahydroligustilide) > senkyunolide I ((E)-6, 7-dihydroxy-6, 7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3, 8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the ((Z)-6, 7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.