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.