Quercetin is one of the most ubiquitous
bioflavonoids in foods of plant origin. Although
quercetin is generally considered to provide protection against oxidative injury and
inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and
inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that
quercetin inhibited [3H]
thymidine incorporation into rat aortic smooth muscle cells only at concentrations < or =50 microM in a concentration-dependent manner. Nevertheless,
quercetin, at concentrations > or =100 microM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of
pro-caspase-3. Additionally, the phosphorylation of
c-Jun N-terminal kinase (JNK) and
p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 microM
quercetin, results which differ from observations by others and ourselves of cells exposed to < or =50 microM
quercetin. Unlike P-JNK and P-p38, the phosphorylation of
extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of
quercetin. Surprisingly, the adverse effects of higher concentrations of
quercetin could be ameliorated by adding the
antioxidants,
catalase, and
N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to
quercetin at concentrations of < or =50 microM caused concentration-dependent inhibition of
nuclear factor kappa B (
NF-kappaB) activity, whereas concentrations of > or =100 microM resulted in increased
NF-kappaB binding activity. We demonstrate for the first time that
quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of > or =100 microM, is likely to induce the opposite effects on rat aortic smooth muscle cells.