Xanthohumol 

Xanthohumol is one of the principal flavonoids isolated from hops, the inhibitor of diacylglycerol acetyltransferase (DGAT), COX-1 and COX-2, and shows anti-cancer and anti-angiogenic activities. Xanthohumol also has antiviral activity against bovine viral diarrhea virus (BVDV), rhinovirus, HSV-1, HSV-2 and cytomegalovirus (CMV).

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 Ca²⁺ sparks and Ca²⁺ waves in control myocytes and in cells subjected to Ca²⁺ 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 Ca²⁺ transients, without suppressing I_Ca, but this effect is small and reversed by isoproterenol at physiological temperatures. Xanthohumol also suppresses the Ca²⁺ 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.

354.40

Solid

C₂₁H₂₂O₅

6754-58-1

O=C(C1=C(OC)C=C(O)C(C/C=C(C)\C)=C1O)/C=C/C2=CC=C(O)C=C2.[(E)]

Room temperature in continental US; may vary elsewhere.

• [1]. Luzak B, et al. Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity. Arch Physiol Biochem. 2016 Nov 18:1-7  [Content Brief]

  [2]. Arnaiz-Cot JJ, et al. Xanthohumol modulates calcium signaling in rat ventricular myocytes: Possible Antiarrhythmic properties. J Pharmacol Exp Ther. 2016 Nov 4. pii: jpet.116.236588  [Content Brief]

  [3]. Gallo C, et al. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation. Oncotarget. 2016 Aug 1  [Content Brief]

  [4]. Chen PH, et al. The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death. Neuropharmacology. 2016 Nov;110(Pt A):362-75.  [Content Brief]

  [5]. Inokoshi J, et al. Expression of two human acyl-CoA:diacylglycerol acyltransferase isozymes in yeast and selectivity of microbial inhibitors toward the isozymes. J Antibiot (Tokyo). 2009;62(1):51-54.  [Content Brief]

  [6]. Buckwold VE, et al. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res. 2004 Jan;61(1):57-62.  [Content Brief]