Chicoric Acid Ameliorates Lipopolysaccharide-lnduced Oxidative Stress via Promoting the Keapl/Nrf2 Transcriptional Signaling Pathway in BV-2 Microglial Cells and Mouse Brain

As a major nutraceutical component of a typical Mediterranean vegetable chicory, chicoric acid (CA) has been well -documented due to its excellent antioxidant and antiobesity bioactivities. In the current study, the effects of CA on lipopolysaccharide (LPS)-stimulated oxidative stress in BV-2 microglia and CS7BL/6J mice and the underlying molecular mechanisms were investigated. Results demonstrated that CA significantly reversed LPS-elicited cell viability decrease, mitochondrial dysfunction, activation of NFKB and MAPK stress pathways, and inflammation responses via balancing cellular redox status. Furthermore, molecular modeling study demonstrated that CA could insert into the pocket of Keapl and up regulated Nrf2 signaling and, thus, transcriptionally regulate downstream expressions of antioxidant enzymes including HO-1 and NQO-1 in both microglial cells and ip injection of LPS-treated mouse brain. These results suggested that CA attenuated LPS-induced oxidative stress via mediating Keapl/Nrf2 transcriptional pathways and downstream enzyme expressions, which indicated that CA has great potential as a nutritional preventive strategy in oxidative stress-related neuroinflammation.