Neuroprotective Effects of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), in Ischemic Stroke of Rats
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- 作者：Ting-Lin Yen ; Chung-King Hsu ; Wan-Jung Lu ; Cheng-Ying Hsieh ; George Hsiao ; Duen-Suey Chou ; Gong-Jhe Wu ; Joen-Rong Sheu
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2012
- 出版时间：February 29, 2012
- 年：2012
- 卷：60
- 期：8
- 页码：1937-1944
- 全文大小：349K
- 年卷期：v.60,no.8(February 29, 2012)
- ISSN：1520-5118
文摘
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)-1伪, tumor necrosis factor (TNF)-伪, 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鈥?0 渭M) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 渭g/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 渭M) markedly reduced the ESR signal intensity of hydroxyl radical (OH鈥?/sup>) 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-1伪, iNOS expression, and free radical formation), apoptosis (i.e., TNF-伪, 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.