Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway

Feb 1, 2022Food & function

Chicoric acid may protect brain cells in Parkinson's mice through gut bacteria and immune signaling

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Abstract

Oral pretreatments of chicoric acid significantly prevented MPTP-induced motor dysfunctions and death of dopaminergic neurons.

Chicoric acid is associated with the inhibition of glial hyperactivation and an increase in neurotrophins in the striatum.
CA significantly reduced microbial dysbiosis induced by MPTP and partially restored gut microbiota composition.
CA promoted the integrity of the colonic epithelium and normalized short-chain fatty acid production.
Proinflammatory cytokines TNF-α and IL-1β were reduced in the serum, striatum, and colon with CA treatment.
Inhibition of the TLR4/MyD88/NF-κB signaling pathway may underlie the anti-inflammatory effects of CA.

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Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (), has been regarded as a nutraceutical to combat inflammation, viruses and obesity. Parkinson's disease (PD) is a common neurodegenerative disorder, and the microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results obtained in this study demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunctions and death of nigrostriatal dopaminergic neurons along with the inhibition of glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of the gut microbiota to normal, including decreased phylumand genera, as well as increased phylum, generaand. Besides, CA promoted colonic epithelial integrity and restored normal SCFA production. We also observed that proinflammatory cytokines such as TNF-α and IL-1β in the serum, striatum and colon were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of the TLR4/MyD88/NF-κB signaling pathway might be the underlying molecular mechanism. These findings demonstrated that CA had neuroprotective effects on MPTP-induced PD mice possiblymodulating the gut microbiota and inhibiting inflammation throughout the brain-gut axis. Echinacea purpurea Bacteroidetes Parabacteroide Firmicutes Lactobacillus Ruminiclostridium via

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Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway

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