Astragaloside IV against Alzheimer's disease via microglia-mediated neuroinflammation using network pharmacology and experimental validation

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.