Abstract
Chicoric acid (CA), a polyphenolic acid compound extracted from chicory and echinacea, possesses antiviral, antioxidative and anti-inflammatory activities. Growing evidence supports the pivotal roles of brain–spleen and brain–gut axes in neurodegenerative diseases, including Parkinson’s disease (PD), and the immune response of the spleen and colon is always the active participant in the pathogenesis and development of PD. In this study, we observe that CA prevented dopaminergic neuronal lesions, motor deficits and glial activation in PD mice, along with the increment in striatal brain-derived neurotrophic factor (BDNF), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HT). Furthermore, CA reversed the level of interleukin-17(IL-17), interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) of PD mice, implicating its regulatory effect on the immunological response of spleen and colon. Transcriptome analysis revealed that 22 genes in the spleen (21 upregulated and 1 downregulated) and 306 genes (190 upregulated and 116 downregulated) in the colon were significantly differentially expressed in CA-pretreated mice. These genes were functionally annotated with GSEA, GO and KEGG pathway enrichment, providing the potential target genes and molecular biological mechanisms for the modulation of CA on the spleen and gut in PD. Remarkably, CA restored some gene expressions to normal level. Our results highlighted that the neuroprotection of CA might be associated with the manipulation of CA on brain–spleen and brain–gut axes in PD.
Highlights
The results revealed that Chicoric acid (CA) possessed neuroprotective effects on the motor function of Parkinson’s disease (PD) mice
A neuroinflammatory response was observed in PD mice, as the glia population increased after being MPTP challenged, which was characterized by higher levels of cluster of differentiation molecule 11b (CD11b), ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP), the hallmarks of activated microglia and astrocytes
To further explore the prominent role of the spleen and gut in PD, and the regulatory effects of CA on them, we investigated transcriptome-level changes in the spleen and colon between the MPTP and CA+MPTP groups to provide a holistic view of genetic networks and demonstrate the molecular mechanism of the spleen and gut for the neuroprotection of CA on PD
Summary
The neuroinflammatory phenotypes of PD can be modulated by peripheral immunoreactions through the molecular crosstalk between resident and blood-derived cellular components, suggesting that peripheral immunity is an active participant in the neuroinflammatory and neurodegenerative progression of PD [3,4,5]. Increased splenic macrophages with activated M1 subtype could induce the systemic proinflammatory response, leading to the neurological damage and motor disorder in a mouse model of parkinsonism [7]. 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced mice treated with an immune modulator exhibited increased splenocytes and spleen size, which suppressed the neuroinflammatory response, motor dysfunctions and dopaminergic neuronal depletion, implicating a mediating role of the spleen in the immunological communication between central nervous system (CNS) and peripheral immune system of PD [8,9,10].
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