Cyclo(his-pro) is an endogenous cyclic dipeptide that exerts oxidative damage protection by selectively activating the transcription factor Nrf2 signalling pathway.

cyclo(His-Pro) inhibits NF-κB nuclear accumulation induced by paraquat in rat pheochromocytoma PC12 cells via the Nrf2/heme oxygenase-1 pathway.?The protection required functional heme oxygenase-1 activity, since zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, prevented NF-κB inhibition, and the presence of exogenous carbon monoxide and bilirubin afforded cytoprotection against paraquat-induced toxicity by preventing NF-κB activation.?Cyclooxygenase-2 and matrix metalloproteinase 3, two gene products governed by NF-κB, were down-regulated by cyclo(His-Pro) and up-regulated in heme oxygenase-1 knock-down cells.?We validated the general mechanism underlying the anti-inflammatory effects by treating PC12 and murine microglial BV2 cells with different pro-inflammatory agents.?Finally, cyclo(His-Pro) reduced 12-otetradecanoylphorbol-13-acetate-induced oedema in mouse ear inflammation model.?Results, by showing that cyclo(His-pro) suppresses the pro-inflammatory NF-κB signalling via the Nrf2-mediated heme oxygenase-1 activation, contribute to the understanding of essential cellular pathways and allow the proposal of cyclo(His-Pro) as an in vivo anti-inflammatory compound[1].