Chicoric acid supplementation prevents systemic inflammation‐induced memory impairment and amyloidogenesis via inhibition of NF‐κB

Chicoric acid (CA), a natural phenolic acid extracted from chicory and the echinacea (purple coneflower) plant (Echinacea purpurea), has been regarded as a nutraceutical that has powerful antioxidant and antiobesity activities. We investigated the inhibitory effects of CA on systemic inflammation-induced neuroinflammation, amyloidogenesis, and cognitive impairment. C57BL/6J mice were treated with 0.05% CA in the drinking water for 45 d. The mice were then treated by intraperitoneal injection of lipopolysaccharide (LPS). It was found that CA prevented LPS-induced memory impairment and neuronal loss through behavioral tests and histological exam-ination. Furthermore, amyloidogenesis in the CNS was detected. The results showed that CA prevented LPS-induced increases in amyloid β (1–42 specific) (Aβ1–42) accumulation, levels of amyloid precursor protein, and neuronal β-secretase 1 (BACE1), as well as the equilibrium cholinergic system in mouse brain. Moreover, CA down-regulated LPS-induced glial overactivation by inhibiting the MAPK and NF-κB pathway. Consequently, CA reduced the levels of NF-κB transcriptionally regulated inflammatory mediators and cytokines such as iNOS, cyclooxygenase-2 (COX-2), IL-1β, and TNF-α in both mouse brain and BV2 microglial cells. These results demonstrated that CA alleviated memory impairment and amyloidogenesis triggered by LPS through suppressing NF-κB transcriptional pathway, suggesting that CA might be a plausible therapeutic intervention for neuroinflammation-related diseases such as Alzheimer disease. —Liu, Q., Chen, Y., Shen, C., Xiao, Y., Wang, Y., Liu, Z., Liu, X. Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-κB. FASEB J. 31, 1494–1507 (2017) www.fasebj.org