quercetin inhibits shc and phosphatidylinositol 3kinasemediated cjun nterminal kinase activation by angiotensin ii in cultured rat aortic smooth muscle cells angiotensin ii ang ii induces vascular smooth muscle cell vsmc hypertrophy which results in various cardiovascular diseases ang iiinduced cellular events have been implicated in part in the activation of mitogenactivated protein map kinases although it has been proposed that daily intake of bioflavonoids belonging to polyphenols reduces the incidence of ischemic heart diseases known as french paradox the precise mechanisms of efficacy have not been elucidated thus we hypothesized that bioflavonoids may affect ang iiinduced map kinase activation in cultured rat aortic smooth muscle cells rasmc our findings showed that ang ii stimulated rapid and significant activation of extracellular signalregulated kinase erk 12 cjun nterminal kinase jnk and p38 in rasmc ang iiinduced jnk activation was inhibited by 33457pentahydroxyflavone quercetin a major bioflavonoid in foods of plant origin whereas erk12 and p38 activation by ang ii were not affected by quercetin ang ii caused a rapid tyrosine phosphorylation of src homology and collagen shc which was inhibited by quercetin quercetin also inhibited ang iiinduced shcp85 association and subsequent activation of phosphatidylinositol 3kinase pi3kakt pathway in rasmc furthermore ly294002 a pi3k inhibitor and a quercetin derivative inhibited ang iiinduced jnk activation as well as akt phosphorylation finally ang iiinduced 3hleucine incorporation was abolished by both quercetin and ly294002 these findings suggest that the preventing effect of quercetin on ang iiinduced vsmc hypertrophy are attributable in part to its inhibitory effect on shc and pi3kdependent jnk activation in vsmc thus inhibition of jnk by quercetin may imply its usefulness for the treatment of cardiovascular diseases relevant to vsmc growth