Xanthohumol significantly attenuates ADP-induced blood platelet aggregation, and significantly reduces the expression of fibrinogen receptor (activated form of GPIIbIIIa) on platelets surface.
Xanthohumol (5-50 nM) reduces the frequency of spontaneously occurring Ca sparks and Ca waves in control myocytes and in cells subjected to Ca overload caused by: (1) exposure to low K solutions, (2) periods of high frequency electrical stimulation, (3) exposures to isoproterenol or (4) caffeine. Xanthohumol (50-100 nM) reduces the rate of relaxation of electrically- or caffeine-triggered Ca transients, without suppressing ICa, but this effect is small and reversed by isoproterenol at physiological temperatures. Xanthohumol also suppresses the Ca content of the SR, and its rate of recirculation.
Treatment of endothelial cells with Xanthohumol leads to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirm that AMPK mediates Xanthohumol anti-angiogenic activity. AMPK activation by Xanthohumol is mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms shows that Xanthohumol-induced AMPK activation reduces nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway is inactivated by Xanthohumol as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously.
Xanthohumol significantly reduces cell viability and induces apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. Pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participate in Xanthohumol-induced glioma cell death. Xanthohumols inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting plays a critical role in mediating glioma cell death.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.