Chicoric acid prevents neurodegeneration via microbiota-gut-brain axis in a mouse Parkinson’s disease model

Abstract

It is determined that microbiota-gut-brain axis is involved in the pathogenesis of Parkinson’s Disease (PD) and may be the potential target for developing the therapeutic treatments for PD. Chicoric acid (CA) is a kind of natural polyphenolic acid compounds which are recognized as promising agents against neurodegenerative disease. Here, we investigated the influence of CA on microbiota-gut-brain axis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mice. The results demonstrated that oral pretreatments of CA significantly prevented the MPTP-indued motor disorders, death of nigrostriatal dopaminergic neurons and reduction in striatal neurotrophins. Sequencing results of 16S rRNA indicated the microbial dysbiosis occurred in MPTP mice, whereas CA exerted a remarkable impact on microbial diversity and microbiota compositions, as well as SCFAs production. Besides, CA pretreatment alleviated gliosis-mediated neuroinflammation and gut inflammation by suppressing TLR4/MyD88/NF-κB signaling cascade, along with preventing the colonic hyperpermeability. To conclude, CA prevented MPTP-induced neuroinflammation and neuronal degenerative processes through signaling multiple pathways of microbiota-gut-brain axis.