Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases in the world. The effective therapeutic methods and drugs are still not clear. Astragaloside IV (AS-IV), a triterpenoid saponin isolated from the root of Huangqi, has a beneficial effect in the treatment of AD. However, whether AS-IV alters microglia in the inflammation of AD is still ambiguous. In our study, 99 common targets were collected between AS-IV and AD. BCL2 apoptosis regulator (Bcl-2), pro-apoptotic BCL-2 protein BAX, epidermal growth factor receptor (EGFR), and receptor tyrosine phosphatase type C (PTPRC) were screened for inflammation and microglia in the above targets by network pharmacology. Interleukin-1β (IL-1β) and EGFR both interact with signal transducer and activator of transcription 3 (STAT3) by a protein interaction network, and IL-1β had a higher affinity for AS-IV based on molecular docking. Enrichment revealed targets involved in the regulation of neuronal cell bodies, growth factor receptor binding, EGFR tyrosine kinase inhibitor resistance., etc. Besides, AS-IV alleviated the reduced cell proliferation in amyloid-beta (Aβ)-treated microglial BV2 cells. AS-IV affected BV2 cell morphological changes and decreased cluster of differentiation 11b (CD11b) gene, IL-1β, and EGFR mRNA levels increment during lipopolysaccharide (LPS) injury in BV2 cell activation. Therefore, AS-IV may regulate microglial activation and inflammation via EGFR-dependent pathways in AD. EGFR and IL-1β are vital targets that may relate to each other to coregulate downstream molecular functions in the cure of AD. Our study provides a candidate drug and disease target for the treatment of neurodegenerative diseases in the clinic.
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