Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells
Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells
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DOI：
10.1016/j.neuint.2010.11.008
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发表时间：
2011-02-01
影响因子：
4.2
通讯作者：
Choi, Hyun Jin
中科院分区：
文献类型：
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作者：
Lee, Ik-Soo;Lim, Juhee;Choi, Hyun Jin
黄腐酚（2 '，4'，4-三羟基-6 '-甲氧基-3'-异戊烯基查耳酮）是从啤酒花（Humulus lupulus L）中分离的主要查耳酮衍生物，由于其苦味而通常用于酿造。黄腐酚具有抗癌、清除自由基和抗炎活性，但其确切机制尚不清楚。碱性亮氨酸拉链（bZIP）蛋白NRF 2是介导动物抗氧化和抗炎反应的关键转录因子。因此，我们测试了黄腐酚是否通过NRF 2信号传导在小鼠小胶质细胞BV 2细胞中发挥抗炎活性。黄腐酚显著抑制炎症介质NO、IL-1 β和TNF-α的过度产生，以及LPS诱导的刺激的BV 2细胞中NF-κ B信号传导的激活。黄腐酚上调NAD（P）H：醌氧化还原酶1（NQO 1）和血红素加氧酶-1（HO-1）的转录，并增加内源性抗氧化剂GSH的水平。此外，黄腐酚诱导NRF 2核转位和进一步激活ARE启动子相关的转录。黄腐酚的抗炎反应减弱与NRF 2 siRNA转染和HO-1抑制剂，ZnPP的存在下，但不是NQO 1抑制剂，双香豆素。综上所述，我们的研究表明，黄腐酚通过NRF 2-ARE信号传导和上调下游HO-1发挥抗炎活性，并且可能是调节脑中炎症反应的有吸引力的候选者。(C)2010爱思唯尔有限公司保留所有权利。
Xanthohumol (2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone) is a major chalcone derivative isolated from hop (Humulus lupulus L) commonly used in brewing due to its bitter flavors. Xanthohumol has anti-carcinogenic, free radical-scavenging, and anti-inflammatory activities, but its precise mechanisms are not clarified yet. The basic leucine zipper (bZIP) protein NRF2 is a key transcription factor mediating the antioxidant and anti-inflammatory responses in animals. Therefore, we tested whether xanthohumol exerts anti-inflammatory activity in mouse microglial BV2 cells via NRF2 signaling. Xanthohumol significantly inhibited the excessive production of inflammatory mediators NO, IL-1 beta, and TNF-alpha, and the activation of NF-kappa B signaling in LPS-induced stimulated BV2 cells. Xanthohumol up-regulated the transcription of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), and increased the level of the endogenous antioxidant GSH. In addition, xanthohumol induced nuclear translocation of NRF2 and further activation of ARE promoter-related transcription. The anti-inflammatory response of xanthohumol was attenuated by transfection with NRF2 siRNA and in the presence of the HO-1 inhibitor, ZnPP, but not the NQO1 inhibitor, dicoumarol. Taken together, our study suggests that xanthohumol exerts anti-inflammatory activity through NRF2-ARE signaling and up-regulation of downstream HO-1, and could be an attractive candidate for the regulation of inflammatory responses in the brain. (C) 2010 Elsevier Ltd. All rights reserved.