ABSTRACT
Aim To investigate the role of naringenin in nuclear factor erythroid 2-related factor 2 (Nrf2)/ phase II detoxifying enzyme activities and evaluate its effects on vascular inflammation. Methods Western blot, immunofluorescence and reverse transcription- qPCR were used to detect the protein expression. The activities of phase II detoxifying enzymes were measured by commercial kits. Immunoprecipitation technology was used to detect the interaction between Nrf2 and kelch-like ECH-associated protein 1 ( Keap-1). Results Naringenin promoted the dislocation of Nr£2 from Keap-1 and increased Nrf2 nuclear accumulation in RAW264. 7 macrophages. Naringenin up-regulated expressions of phase II detoxifying enzymes such as NAD(P)H quinone oxidoreductase ( NQO-1), gluta thione S-transferase (GST) and glutamate-cysteine lig- ase (GCL). It also reduced the levels of cytokines in macrophages. Moreover, the Nrf2 inhibitor ML385 reduced phase II detoxifying enzyme expressions and increased cytokine levels. In addition, we found naringenin increased the expressions and activities of liver phase II detoxifying enzymes ( NQO-1, GST and GCL) and reduced aortic inflammation in atherosclerotic model mice. The effects were dependent on Nr£2 activity. Conclusions Naringenin activates Nrf2 and promotes phase II detoxifying enzyme activities, which leads to the inhibition of vascular inflammation.