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.

Automated summary

The study found that the styryl flavonoid 6-PN could inhibit the generation of pro-inflammatory cytokines and reactive oxygen species (ROS) by downregulating the protein levels of AGE receptor (RAGE) and NADPH oxidase, improving the damage caused by AGE to cells. Compared to its parental compound, 6-PN showed higher bioavailability. Additionally, 6-PN inhibited AGE-induced inflammation through the activation of the Nrf2 signaling pathway, and this anti-inflammatory effect was blocked by the Nrf2 inhibitor.