Neuroprotective Effects of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), in Ischemic Stroke of Rats

Abstract

Xanthohumol is the principal prenylated flavonoid in hops (Humulus lupulus L.), an ingredient of beer. Xanthohumol was found to be a potent chemopreventive agent; however, no data are available concerning its neuroprotective effects. In the present study, the neuroprotective activity and mechanisms of xanthohumol in rats with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia were examined. Treatment with xanthohumol (0.2 and 0.4 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Xanthohumol treatment produced a marked reduction in infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions in ischemic regions. These expressions were obviously inhibited by treatment with xanthohumol. In addition, xanthohumol (3-70 μM) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 μg/mL) in human platelet-rich plasma. An electron spin resonance (ESR) method was used to examine the scavenging activity of xanthohumol on free radicals which had formed. Xanthohumol (1.5 and 3 μM) markedly reduced the ESR signal intensity of hydroxyl radical (OH•) formation in the H₂O₂/NaOH/DMSO system. In conclusion, this study demonstrates for the first time that in addition to its originally being considered an agent preventing tumor growth, xanthohumol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1α, iNOS expression, and free radical formation), apoptosis (i.e., TNF-α, active caspase-3), and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, this novel role of xanthohumol may represent high therapeutic potential for treatment or prevention of ischemia-reperfusion injury-related disorders.

Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release

“…Furthermore, XN treatment significantly improved blood viscosity in rats. These results suggest that XN may have great potential as an anti-thrombotic drug and are consistent with published reports stating that beer at moderate levels may protect against thrombosis and XN reduce infarct volume in rats with cerebral ischemia [10,11,51]. A well-known major limitation of current antithrombotic therapies is their inability to separate bleeding occurrences from thrombotic events as well as various serious side effects [6].…”

Xanthohumol improved cognitive flexibility in young mice

“…Xanthohumol is a prenylated calconoid that is a part of the flavonoid family. Treatment with xanthohumol has been shown to be neuroprotective in stroke-induced rats [69]. Recent evidence found that derivatives of xanthohumol can induce neurite growth in mouse neuronal cells [70].…”

Dose- and Time-Dependent Neuroprotective Effects of Pycnogenol® following Traumatic Brain Injury

“…24 PYC is a patented combination of bioflavonoids extracted from the bark of French maritime pine tree (Pinus maritima) and has a high capacity to scavenge free radicals and promote cellular health. Bioflavonoids are natural compounds that are known as neuroprotective agents, due in part to their antioxidant and antiinflammatory properties 25 and their ability to modulate intracellular signaling. 26 In our previous study, animals were treated with multiple high intraperitoneal doses of PYC immediately after the trauma.…”