Chicoric Acid Prevents Neuroinflammation and Neurodegeneration in a Mouse Parkinson’s Disease Model: Immune Response and Transcriptome Profile of the Spleen and Colon

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.

Chicoric Acid Alleviates Colitis via Targeting the Gut Microbiota Accompanied by Maintaining Intestinal Barrier Integrity and Inhibiting Inflammatory Responses

“…In addition, a recent study showed that CA reverses the levels of interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in mice. The potential targets and mechanisms of CA regulating spleen and intestinal immune response were elucidated by analyzing the expression of differential genes using transcriptomics . This suggests that we can further explore the molecular mechanism and key targets of CA in alleviating colitis from the perspective of immunity in the future.…”

Echinacea purpurea extract intervention for counteracting neurochemical and behavioral changes induced by bifenthrin

“…Velíšek (2006) stated that Echinacea extract counteracted dopamine, acetylcholine, opioids, and the GABAergic system in the brain; interestingly, Konishi et al (2005) and Woelkart et al (2009) attributed this effect to the active components inside the extract such as cafeic acid, rosmarinic acid, and alkamide that can easily pass through the blood-brain barrier and exert their protective effect. Also, the study of Wang et al (2022) indicated that chicoric acid can prevent dopaminergic lesions, motor de cits and glial activation in mice with Parkinson disease, and increase neurotrophic factor, dopamine, and serotonin levels in brain striatum.…”

Chicoric Acid Ameliorated Beta-Amyloid Pathology and Enhanced Expression of Synaptic-Function-Related Markers via L1CAM in Alzheimer’s Disease Models

“…Non-transgenic male mice were used as the wild-type (WT) mice, in parallel with only the male 5xFAD mice. The mice were assigned to four groups ( n = 10/group): the intragastrically injected WT (phosphate buffer solution (PBS)) group, the 5xFAD (PBS) group, the 5xFAD + CA group (40 mg/kg) group, and the WT + CA (40 mg/kg) group [ 11 ]. The CA dose of 40 mg/kg was chosen based on previous studies which showed that CA induces a therapeutic effect, and that there is no toxicity at this dose.…”

“…It has exhibited extensive pharmacological effects, such as regulating glycolipid metabolism and reducing inflammation, oxidation and aging [ 10 ]. It was shown that CA prevented dopaminergic neuropathy, motor deficit and glial activation in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) in mice [ 11 ]. CA has also displayed neuroprotective effects in a mouse model of PD via modulation of the gut microbiota and TLR-4 signaling pathway [ 12 ].…”