Study of the multitarget mechanism of Astragalus (HUANGQI) in the treatment of Alzheimer's disease based on network pharmacology and molecular docking technology.

ABSTRACT

CONTEXT In China, HUANGQI is widely used for the treatment of Alzheimer's disease (AD). However, a comprehensive understanding of its mechanism of anti-AD effects is lacking. OBJECTIVE: To explore the active ingredients of HUANGQI and its potential targets and mechanisms of action in AD. MATERIALS AND METHODS: The active ingredients and targets of HUANGQI were screened from databases (TCSMP, ETCM, and BATMan), and AD-related genes were obtained from DrugBank and GeneCards. The same target genes were screened, and a drug-target disease network was constructed. The PPI network was constructed and GO and KEGG pathway enrichment analyses of the targets. The Cell Counting Kit-8 (CCK-8) assay was used to determine suitable HUANGQI treatment concentrations for HT-22 cells between 0-480 µg/mL. CCK-8, FITC-phalloidin and propidium iodide (PI) assays were used to examine the protective effect of (0, 60, 120, 240 µg/mL) of HUANGQI on 20 µM Aß1-42-induced HT-22 cell cytotoxicity. RESULTS: Twelve active ingredients of HUANGQI were selected, with 679 common targets associated with AD. GO and KEGG analysis revealed that the therapeutic mechanisms of HUANGQI involve TNF, AGE, the NF-κB pathway, and nuclear receptor activity-related processes. The CCK-8 assay indicated that HUANGQI was not cytotoxic to HT-22 cells at concentrations less than 240 µg/mL and was able to attenuate Aß1-42-induced cellular damage (EC50 = 83.46 µg/mL). FITC-phalloidin and PI assays suggested that HUANGQI could alleviate 20 µM Aß1-42-induced neuronal cell cytotoxicity in a dose-dependent manner. CONCLUSION: HUANGQI has a protective effect on Aß1-42-induced nerve cell injury; further mechanism research was needed.