title: Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells.
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.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757, South Korea.
authors.forename: Ik-Soo
authors.initials: IS
authors.lastname: Lee
authors.forename: Juhee
authors.initials: J
authors.lastname: Lim
authors.forename: Jiyeong
authors.initials: J
authors.lastname: Gal
authors.forename: Jeen Chu
authors.initials: JC
authors.lastname: Kang
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005911:Gliosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000502:physiology*; D011427:Propiophenones / Q000494:pharmacology* / Q000627:therapeutic use; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D033921:Vesicular Transport Proteins
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D018836:Inflammation Mediators; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011427:Propiophenones; D011506:Proteins; D033921:Vesicular Transport Proteins; C485462:Vps52 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C104536:xanthohumol