Compounds isolated from Psoralea corylifolia seeds inhibit protein kinase activity and induce apoptotic cell death in mammalian cells.

OBJECTIVES: Psoralea corylifolia is a plant widely used in traditional Chinese medicine, e.g. for its chemopreventive effect. To identify active substances responsible for this effect, we investigated pharmacological effects of 11 compounds isolated from the seeds of this plant (newly described substances: 7, 2', 4'-trihydroxy-3-arylcoumarin and psoracoumestan). METHODS: The influence of distinct compounds on different signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) was screened via analysis of the activity of 24 protein kinases, mitogen activated protein kinase phosphorylation via Western blot, cytotoxicity was shown using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and determination of caspase activity. Oxidative stress was detected via 2',7'-dichlorofluorescein fluorescence. KEY FINDINGS: Some compounds showed cytotoxic effects (H4IIE, Hct116, C6 cells) mainly mediated via induction of apoptosis. Distinct compounds caused a strong inhibition of MAPK/ERK kinase (MEK) phosphorylation, weak effects on extracellular-signal regulated kinase (ERK) phosphorylation and no significant effect on p38 and c-Jun amino-terminal kinase. Corylifol C and, to a lesser extent, xanthoangelol are potent protein kinase inhibitors (inhibitory concentration 50% values for epidermal growth factor receptor (EGFR): 1.1 and 4.4 × 10(-6) µg/ml, respectively). Because EGFR, MEK and ERK are kinases involved in cellular proliferation, an inhibition of these enzymes may be useful to cause chemopreventive effects. CONCLUSIONS: Distinct compounds isolated from P. corylifolia showed a high potential to influence cellular pathways, e.g. by inhibition of protein kinases that may be interesting for pharmacological purposes.

Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin.

The health beneficial effects of a diet rich in fruits and vegetables are, at least in part, attributed to polyphenols that are present in many herbal edibles. Although many in vitro studies revealed a striking variety of biochemical and pharmacological properties data about the beneficial effects of polyphenols in whole organisms, especially with respect to ageing, are quite limited. We used the well established model organism Caenorhabditis elegans to elucidate the protective effects of quercetin, the main representative of the flavonol class of polyphenols, in vivo. Quercetin is taken up by the worms, enhanced the resistance to oxidative stress and prolonged the mean lifespan of C. elegans by 15%. Quercetin was shown to be a strong radical scavenger possibly explaining the observed down-regulation of mitochondrial manganese superoxide dismutase by a reduced need for this antioxidant enzyme for maintenance of cellular redox homeostasis. Quercetin treatment also led to a translocation of the C. elegans FoxO transcription factor DAF-16 into the nucleus, a state often correlated with stress response and longevity. According to our results we suggest that the protective and life prolonging action of quercetin is not only due to its strong antioxidant capacity but may also be mediated by modulation of signalling pathways.