title: Chicoric Acid Ameliorates Lipopolysaccharide-Induced Oxidative Stress via Promoting the Keap1/Nrf2 Transcriptional Signaling Pathway in BV-2 Microglial Cells and Mouse Brain.
abstract: 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 C57BL/6J mice and the underlying molecular mechanisms were investigated. Results demonstrated that CA significantly reversed LPS-elicited cell viability decrease, mitochondrial dysfunction, activation of NFκB 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 Keap1 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 Keap1/Nrf2 transcriptional pathways and downstream enzyme expressions, which indicated that CA has great potential as a nutritional preventive strategy in oxidative stress-related neuroinflammation.
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Youfang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University , Yangling, China.
authors.forename: Xuebo
authors.identifier: http://orcid.org/0000-0001-6370-2868
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013386:Succinates / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D013386:Succinates; C100435:chicoric acid
keywords: Keap1/Nrf2; chicoric acid; lipopolysaccharide; microglia; oxidative stress