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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

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

Abstract Source:

Neurochem Int. 2011 Feb ;58(2):153-60. Epub 2010 Nov 18. PMID: 21093515

Abstract Author(s):

Ik-Soo Lee, Juhee Lim, Jiyeong Gal, Jeen Chu Kang, Hyun Jung Kim, Bok Yun Kang, Hyun Jin Choi

Article Affiliation:

Ik-Soo Lee

Abstract:

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-α, 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.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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