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.
Kobayashi
S
S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Mimura
Y
Y
Naitoh
T
T
Kimura
I
I
Kimura
M
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic; D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D010796:Phthalic Anhydrides; C027820:ligustilide; C045855:3-N-butyl-4,5-dihydrophthalide; D015107:4-Butyrolactone; C026105:butylidenephthalide