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].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

354.40

C₂₁H₂₂O₅

6754-58-1

Room temperature in continental US; may vary elsewhere.

DMSO : 83.33 mg/mL (235.13 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (5.87 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.87 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (5.87 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.87 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [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

  [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

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

  [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.

  [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.

  [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.

In vitro cell proliferation/viability is measured by the MTT test at different time points. 1000 cells/well are plated into 96-multiwell plates in complete medium. Following adhesion, medium is replaced with fresh medium containing the different treatments or vehicle (DMSO in medium). Xanthohumol and EGCG are used in a concentration range from 2.5 to 40 μM, up to 96 hours. 3 hours before each time point, MTT reagent (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) is added to the wells and plates are incubated at 37°C. At the indicated time points, absorbance at 540 nm is then measured by a FLUOstar spectrophotometer.

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

• [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

  [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

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

  [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.

  [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.

  [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.