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首页> 外文期刊>Journal of Agricultural and Food Chemistry >Neuroprotective Effects of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), in Ischemic Stroke of Rats
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Neuroprotective Effects of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), in Ischemic Stroke of Rats

机译：啤酒花中异黄酮类黄酮黄腐酚对大鼠缺血性中风的神经保护作用

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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; intraperitonealiy) 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 ^M.) 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-reperflision injury-related disorders.
机译：Xanthohumol是啤酒花中啤酒花的主要异黄酮类黄酮（Humulus lupulus L.）。发现黄腐酚是一种有效的化学预防剂。但是，尚无有关其神经保护作用的数据。在本研究中，研究了黄嘌呤酚对大脑中动脉阻塞（MCAO）引起的脑缺血大鼠的神经保护活性和机制。 MCAO剂量依赖前10分钟用黄腐酚（0.2和0.4 mg / kg;腹膜内）治疗可减轻局灶性脑缺血并改善脑缺血大鼠的神经行为缺陷。与对照大鼠相比，黄腐酚治疗使梗塞面积明显减少。 MCAO诱导的局灶性脑缺血与缺血区域缺氧诱导因子（HIF）-1α，肿瘤坏死因子（TNF）-α，诱导型一氧化氮合酶（iNOS）和活性caspase-3蛋白表达增加有关。黄嘌呤酚处理明显抑制了这些表达。此外，在富含血小板的人血浆中，黄腐酚（3-70μM）浓度依赖性地抑制了胶原蛋白（1μg/ mL）刺激的血小板聚集。电子自旋共振（ESR）方法用于检查黄腐酚对已形成的自由基的清除活性。黄腐酚（1.5和3 ^ M。）显着降低了H2O2 / NaOH / DMSO系统中羟基自由基（OH *）形成的ESR信号强度。总之，这项研究首次证明，除最初被认为是预防肿瘤生长的药物外，黄腐酚具有强大的神经保护活性。该活性至少部分地通过抑制炎症反应（即HIF-1α，iNOS表达和自由基形成），凋亡（即TNF-α，活性caspase-3）和血小板活化而介导。可以减少脑缺血大鼠的梗塞体积并改善其神经行为。因此，黄腐酚的这种新作用可能代表用于治疗或预防缺血再反射性损伤相关疾病的高治疗潜力。

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