6-C-(E-Phenylethenyl)-naringenin, a Styryl Flavonoid, Inhibits Advanced Glycation End Product-Induced Inflammation by Upregulation of Nrf2.

Styryl flavonoids can be formed during the thermal processing of meats and flavonoid-enriched foods, showing high potentials in the prevention of different diseases. In this study, the protective effects of several styryl flavonoids against advanced glycation end product (AGE)-induced inflammation were evaluated, with 6-C-(E-phenylethenyl)-naringenin (6-PN) showing the strongest activity among them. The results indicated that 6-PN significantly ameliorated AGE-induced damages in human umbilical vein endothelial cells, including inhibition of pro-inflammatory cytokines and reactive oxygen species (ROS) production through downregulating the protein levels of the receptor for AGEs (RAGE) and NADPH oxidase. Notably, 6-PN possessed a much higher bioavailability than its parental compound, naringenin. Furthermore, 6-PN also promoted the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway that was suppressed by AGEs, and the anti-inflammatory effects of 6-PN disappeared when the cells were treated with ML385, a Nrf2 inhibitor. Hence, 6-PN might inhibit AGE-induced inflammation by the RAGE/ROS/Nrf2 signaling pathway.