Astrapterocarpan isolated from Astragalus membranaceus inhibits proliferation of vascular smooth muscle cells.
The inhibitory effects of astrapterocarpan, formononetin, and calycosin isolated from Astragalus membraneceus on platelet-derived growth factor (PDGF)-BB-induced proliferative response in rat vascular smooth muscle cells (A10 cells) were investigated. Astrapterocarpan significantly inhibited PDGF-BB-induced cell proliferation and DNA synthesis in a concentration-dependent manner. This inhibition was not attributed to toxicity. In contrast, formononetin and calycosin had no effect. We next examined the effect of astrapterocarpan on PDGF-BB signal transduction. Astrapterocarpan inhibited PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERIC1/2) mitogen-activated protein (MAP) kinase. However, this compound had no effect on phosphorylation of PDGF-beta-receptor, Akt kinase and p38 MAP kinase. These results indicated that astrapterocarpan inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and that this effect may be mediated, at least in part, by inhibition of the ERK1/2 MAP kinase cascade.
Ohkawara
Susumu
S
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Okuma
Yasunobu
Y
Uehara
Takashi
T
Yamagishi
Takashi
T
Nomura
Yasuyuki
Y
D000818:Animals; D001011:Aorta; D027885:Astragalus propinquus / Q000737:chemistry*; D000077214:Becaplermin; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D007529:Isoflavones / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D036343:Pterocarpans / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007529:Isoflavones; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D036343:Pterocarpans; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D000077214:Becaplermin; C007768:formononetin; D014443:Tyrosine; D020797:Receptor, Platelet-Derived Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3