[Shenzao Jiannao Oral Liquid suppresses NF-κB signaling pathway to alleviate neuroinflammation in Alzheimer's disease].

This study aims to use network pharmacology methods and animal experiments to decipher the mechanism by which Shenzao Jiannao Oral Liquid treats Alzheimer's disease(AD). Firstly, a mouse model of AD was established with APP/PS1 mice. Mice were assigned into 6 groups(n=10): blank, model, positive drug(donepezil hydrochloride, 0.65 mg·kg~(-1)), and low-, medium-, and high-dose(0.3, 1.5, and 7.5 g·kg~(-1), respectively) Shenzao Jiannao Oral Liquid, and administrated with corresponding agents by gavage for 28 days. Morris water maze and Y maze were used to evaluate the effects of Shenzao Jiannao Oral Liquid on the learning and memory abilities of mice. Hematoxylin-eosin and Nissl staining methods were used to detect pathological damage in mouse brain tissue. Secondly, network pharmacology methods were used to construct a "Shenzao Jiannao Oral Liquid active ingredient-AD-target" network by searching databases such as TCMSP, BATMAN, UniProt, OMIM, and GeneCards. STRING was used for Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Lastly, the immunofluorescence method and Western blot were employed to determine the expression of tumor necrosis factor(TNF)-α, interleukin(IL)-1β, synaptophysin(SYN), postsynaptic density protein 95(PSD95), and nuclear factor kappaB(NF-κB) signaling pathway proteins. The results showed that compared with the model group, the high-dose Shenzao Jiannao Oral Liquid group showed significantly shortened escape latency and swimming distance, significantly increased platform crossings, neat arrangement of neurons in the hippocampus, increased Nissl bodies, and restored cell morphology. The network pharmacology methods screened out 129 active ingredients of Shenzao Jiannao Oral Liquid, which shared 70 common targets with AD. The KEGG enrichment results suggested that Shenzao Jiannao Oral Liquid ameliorated AD by regulating the dopaminergic synaptic transmission, TNF signaling pathway, and NF-κB signaling pathway. Furthermore, Shenzao Jiannao Oral Liquid groups showed significantly down-regulated expression levels of TNF-α, IL-1β, and NF-κB signaling pathway proteins and up-regulated expression levels of SYN and PSD95. The results verify that Shenzao Jiannao Oral Liquid can alleviate the cognitive impairment and pathological changes in the brain tissue of AD mice by inhibiting the activation of the NF-κB signaling pathway, reducing inflammation, and enhancing synaptic plasticity.