Prunus mahaleb fruit extract prevents chemically induced colitis and enhances mitochondrial oxidative metabolism via the activation of the Nrf2 pathway.

Scope Polyphenols exhibit their antioxidant activity downstream the activation of the Nuclear factor erythroid 2-related factor 2 pathway (Nrf2) but their ability to modulate lipid metabolism via this mechanism has been limitedly investigated. We hypothesized that flavonoids-rich concentrated extract from Prunus mahaleb(mcfe) may improve oxido-reductive homeostasis and modulate hepatic lipid metabolism via Nrf2. Methods & Results Mcfe ability to enhance the activity of Nrf2-mediated antioxidant/detoxifying enzymes was examined in liver and colon of BALB/c mice upon a 4-weeks supplementation. Macroscopic, histological and biochemical signs of colitis were examined in mouse colon pulsed with 5% (w/v) Dextran Sodium Sulphate(DSS) at the end of mcfe treatment. Untreated or DSS-supplemented mice were used negative or positive control. Mcfe effect on liver lipid metabolism was investigated and the possible link between with the Nrf2 pathway was finally examined. Mcfe intake increased antioxidant defenses in mice colon and its pre-treatment blunted pathological signs of colitis, as compared to positive control. In the liver, the increase in antioxidant defenses was associated with enhanced oxidative metabolism and with higher levels of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1alpha) and of hemeoxygenase-1(HO-1), in comparison with negative controls. Conclusion Cytoprotective and hypolipidemic effect produced by mcfe intake are, at least in part, associated with the activation of the Nrf2 pathway.