Luteolin and Apigenin Attenuate 4-Hydroxy-2-Nonenal-Mediated Cell Death through Modulation of UPR, Nrf2-ARE and MAPK Pathways in PC12 Cells.

摘要: Luteolin and apigenin are dietary flavones exhibit a broad spectrum of biological activities including antioxidant, anti-inflammatory, anti-cancer neuroprotective effects. The lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE) has been implicated as causative agent in the development neurodegenerative disorders. This study investigates cytoprotective effects luteolin against 4-HNE-mediated cytotoxicity neuronal-like catecholaminergic PC12 cells. Both restored cell viability repressed caspase-3 PARP-1 activation 4-HNE-treated also mitigated LC3 conversion reactive oxygen species (ROS) production. up-regulated unfolded protein response (UPR), leading to an increase endoplasmic reticulum chaperone GRP78 decrease expression UPR-targeted pro-apoptotic genes. They induced Nrf2-targeted HO-1 xCT absence 4-HNE, but counteracted their presence 4-HNE. Moreover, we found that JNK p38 MAPK inhibitors significantly antagonized by apigenin. Consistently, enhanced phosphorylation was observed luteolin- apigenin-treated In conclusion, this result shows activate Nrf2 signaling, which elicit adaptive cellular stress pathways, restore 4-HNE-induced ER homeostasis inhibit cytotoxicity. exerts stronger effect than possibly due its higher MAPK, UPR activation, ROS scavenging activity.