P-coumaric acid ameliorates Aβ25–35-induced brain damage in mice by modulating gut microbiota and serum metabolites

• DOI: 10.1016/j.biopha.2023.115825
• Publication Date: 2023-11-02T15:39:08Z
• Authors: Bing Cao; Meng-nan Zeng; Feng-xiao Hao; Zhi-you Hao; Zhen-kai Zhang; Xi-wen Liang; Yuan-yuan Wu; Yu-han Zhang; Wei-sheng Feng; Xiao-ke Zheng
• Keywords: 0301 basic medicine; Glucose Transporter Type 1; Amyloid beta-Peptides; NF-kappa B; Brain; Neurodegenerative Diseases; Gastrointestinal Microbiome; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Glucose; Alzheimer Disease; Neuroinflammatory Diseases; Animals; Proto-Oncogene Proteins c-akt

Alzheimer's disease (AD) is a progressive neurodegenerative for which there lack of effective therapeutic drugs. There great potential natural products to be used in the development anti-AD P-coumaric acid (PCA), small molecule phenolic widely distributed plant kingdom, has pharmacological effects such as neuroprotection, but its mechanism not been fully elucidated. In current study, we investigated PCA intervention Aβ25-35-induced AD model using gut microbiomics and serum metabolomics combined with vitro vivo experiments. was found ameliorate cognitive dysfunction neuronal cell damage Aβ25-35-injected mice measured by behavioral, pathological biochemical indicators. 16S rDNA sequencing showed that reduced abundance pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter serratia) gut, were closely associated metabolites glucose metabolism, arachidonic tyrosine metabolism phospholipid pathways serum. Next, investigations revealed regulated disruption through activation PI3K/AKT/Glut1 signaling. Additionally, ameliorated neuroinflammation inhibiting nuclear translocation NF-κB modulating upstream MAPK conclusion, deficits regulating neuroinflammation, related only restoring homeostasis metabolites, also MAPK/NF-κB