Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 108, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.108756
Keywords
VCI; Andrographolide; Network pharmacology; BCCAO; MAPK
Categories
Funding
- National Natural Science Foundation of China [81871103, 81870952, 81974158]
- National Facility for Translational Medicine (Shanghai) [TMSK-2020-122]
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Andrographolide shows potential effects in improving vascular cognitive impairment, possibly by reducing neuroinflammation and enhancing neuronal survival through the inhibition of the MAPK pathway.
Vascular cognitive impairment (VCI) is the second most common form of dementia. Andrographolide (Andro) shows potential effects in anti-inflammation, anti-oxidative stress, and anti-apoptosis. We have obtained 48 potential genes related to the effect of Andro on VCI through network pharmacology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to reveal significant enriched pathway of potential genes, and the mitogen-activated protein kinase (MAPK) pathway was screened out. To verify the results of network pharmacology, we tested the effects of Andro in VCI model induced by bilateral common carotid artery occlusion (BCCAO) surgery. The results showed that Andro treatment ameliorated the cognitive impairment induced by BCCAO. Immunohistochemistry study revealed that Andro could reduce neuronal damage and activation of microglia in the cortex and hippocampus in BCCAO rats. To test the MAPK pathway changes, we analyzed the expression of JNK, p38 and ERK and found that Andro reduced the levels of phosphorylated-ERK (p-ERK) and phosphorylated-p38 (p-p38) in BCCAO rats. In conclusion, Andro could improve neuronal survival, reduce neuroinflammation and ameliorate cognitive impairment in VCI. The underlying mechanisms of Andro treatment may be through the inhibition of MAPK pathway.
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