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

Abstract

Chicoric acid (CA), a natural phenolic acid extracted from chicory and the echinacea (purple coneflower) plant (), 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 examination. Furthermore, amyloidogenesis in the CNS was detected. The results showed that CA prevented LPS-induced increases in amyloid β (1-42 specific) (Aβ) 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 inhibition of NF-κB.

Neuroprotective effect of mogrol against Aβ1–42-induced memory impairment neuroinflammation and apoptosis in mice

“…To study the pharmacological effects of morgrol on the overactivated microglia in hippocampus induced by Aβ 1–42 , the Iba1‐positive cells (overactivated microglia) in hippocampus of mice were detected, the results showed that mogrol (20, 40, 80 mg/kg) can significantly decrease the number of the Iba1‐positive cells. NF‐κB is the central master of regulating the expression of inflammatory mediator genes and aforementioned proinflammatory cytokines . It was proved that downregulation of NF‐κB signal pathway showed neuron protection effects in vitro and in vivo .…”

“…NF-jB is the central master of regulating the expression of inflammatory mediator genes and aforementioned proinflammatory cytokines. [8] It was proved that downregulation of NF-jB signal pathway showed neuron protection effects in vitro and in vivo. [10] It was also proved that downregulation of NF-jB transcriptional activity in the microglial nucleus can reduce the proinflammatory cytokine.…”

“…[3] Among all the Abs, Ab 1-42 peptide is the most abundant one and is deposited early and selectively in the brains of AD patients, [4,5] Ab 1-42 always be considered has a causal role in AD. [6] For experimental research, Ab could induce neuroinflammation and neuronal apoptosis, [7][8][9][10] Ab 1-42 also could stimulate the transcription factor NF-jB, so to cause neuroinflammation. [8,10] In experimental research, Ab has been shown to generate tau protein hyperphosphorylation and Neurofibrillary tangles (NFTs), which will accelerate cognitive deficits.…”

“…[6] For experimental research, Ab could induce neuroinflammation and neuronal apoptosis, [7][8][9][10] Ab 1-42 also could stimulate the transcription factor NF-jB, so to cause neuroinflammation. [8,10] In experimental research, Ab has been shown to generate tau protein hyperphosphorylation and Neurofibrillary tangles (NFTs), which will accelerate cognitive deficits. [11] It was also proved that injecting Ab 1-42 into the animal brain could activate microglial, the major immune cells in the central nervous system, the activated microglial then induced neuronal injury due to the secretion of various proinflammatory molecules such as tumour necrosis factor-a (TNF-a), reactive oxygen species (ROS), interleukin-6 (IL-6), IL-1b.…”

L’heure du changement ?

“…L'acide chicoréique (AC), métabolite secondaire des échinacées ne semblait pas avoir d'importance pharmacologique à côté de l'échinacoside et des polysaccharides. Aujourd'hui, on reconnaît à l'AC un effet anti-inflammatoire dans l'arthrite rhumatismale, mais aussi dans la neuro-inflammation [2], et il peut être bénéfique dans l'amyloïdogenèse et la déficience cognitive. Une supplémentation de 0,05 % d'AC dans de l'eau de boisson chez la souris pendant 45 jours induit une résistance aux effets délétères du lipopolysaccharide sur le cerveau (accumulation de substance β-amyloïde, augmentation des niveaux de la protéine précurseur à l'amyloïde, de la neuronal β-sécrétase 1 [BACE1]).…”