xanthohumol and Stroke

Treatment of antioxidants is necessary to protect ischemic stroke associated neuronal damage. Xanthohumol (XN), a natural flavonoid extracted from hops, has been reported to have potential function as an antioxidant and can be used for neuro protection. However, the role of XN in ischemic stroke remains unclear. Here, we studied the neuroprotective effects of XN through experimental stroke models. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) was used as in vivo and in vitro model, respectively. We found that the treatment of XN improved MCAO-induced brain injury by reducing infarct size, improving neurological deficits, reversing neuronal damage, reducing oxidative stress injury and cell apoptosis. Further experimental studies showed that XN could revive neuronal apoptosis induced by OGD by preventing oxidative stress injury. In addition, our study suggested that these effects were related to the inhibition of phosphorylation of p38-MAPK and the mediation of nuclear Nrf2 activation. In conclusion, the neuroprotective effects of XN showed in this study make XN a promising supplement for ischemic stroke protection.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Flavonoids; Infarction, Middle Cerebral Artery; Male; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Primary Cell Culture; Propiophenones; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke

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.

Topics: Animals; Brain Ischemia; Flavonoids; Free Radical Scavengers; Humulus; Inflorescence; Male; Propiophenones; Rats; Rats, Wistar; Reperfusion Injury; Stroke