[CAS NO. 6754-58-1]  Xanthohumol

Xanthohumol significantly attenuates ADP-induced blood platelet aggregation, and significantly reduces the expression of fibrinogen receptor (activated form of GPIIbIIIa) on platelets' surface ^[1] .
Xanthohumol (5-50 nM) reduces the frequency of spontaneously occurring Ca ²⁺ sparks and Ca ²⁺ waves in control myocytes and in cells subjected to Ca ²⁺ 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 ²⁺ transients, without suppressing I _Ca , but this effect is small and reversed by isoproterenol at physiological temperatures. Xanthohumol also suppresses the Ca ²⁺ content of the SR, and its rate of recirculation ^[2] .
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 ^[3] .
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. Xanthohumol's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting plays a critical role in mediating glioma cell death ^[4] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.