title: Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury.
abstract: Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.
authors.affiliation: Center of Drug Research, Department of Pharmacy, University of Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartkorn
authors.forename: Florian
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Hussam
authors.initials: H
authors.lastname: Ajamieh
authors.forename: Susanne
authors.initials: S
authors.lastname: Vogel
authors.forename: Jörg
authors.initials: J
authors.lastname: Heilmann
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gerbes
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Vollmar
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011427:Propiophenones / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D016328:NF-kappa B; D011427:Propiophenones; D014409:Tumor Necrosis Factor-alpha; C104536:xanthohumol