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.