Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells

详细信息    查看全文

• 作者：Ik-Soo Lee¹ ; ^a ; Juhee Lim¹ ; ^a ; Jiyeong Gal^a ; Jeen Chu Kang^a ; Hyun Jung Kim^a ; Bok Yun Kang^a ; Hyun Jin Choi ; ^a ; ^{hjchoi3@chonnam.ac.kr}
• 关键词：Anti-inflammation ; BV2 ; Heme oxigenase-1 ; Microglia ; Nrf2 ; Xanthohumol
• 刊名：Neurochemistry International
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：58
• 期：2
• 页码：153-160
• 全文大小：563 K

文摘

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-1β, and TNF-;1;, and the activation of NF-κB 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.