Integrated bioinformatics, network pharmacology, molecular docking, and molecular dynamics simulation to explore the potential pharmacological mechanism of Erigeron breviscapus (Vant.) Hand-Mazz regulating ferroptosis for the treatment of Alzheimer's disease

Abstract

Ferroptosis plays a role in Alzheimer's disease (AD) development. Erigeron breviscapus (Vant.) Hand-Mazz (EBHM) shows promising effects in treating cognitive impairment-related diseases. However, the mechanisms by which EBHM regulates ferroptosis in AD treatment are not fully understood. This study used bioinformatics, network pharmacology, molecular docking, and molecular dynamics simulation to explore how EBHM regulates ferroptosis in AD treatment. The results identified four key genes—HSPA8, GSK3B, CTSB, and YWHAG—that are involved in this regulation, and constructed a multigene diagnostic model for AD. The model demonstrated moderate accuracy (area under the curve [AUC] = 0.636) in distinguishing AD from non-demented (ND) and was further validated with external datasets showing good diagnostic capabilities (AUC values of 0.898, 0.889, 0.746, and 0.712). Additionally, CIBERSORT analysis revealed a significant correlation between immune cell infiltration and these four genes, highlighting their potential role in AD immunity. Molecular docking studies indicated that 3,4,5-tricaffeoylquinic acid (TCQA) had the highest binding affinity to HSPA8, suggesting that TCQA and HSPA8 are key components and core targets in EBHM's regulation of ferroptosis in AD therapy. Molecular dynamics simulations confirmed the stability and strong binding affinity of the TCQA-HSPA8 complex. These findings enhance our understanding of the molecular mechanisms underlying ferroptosis regulation by EBHM for the treatment of AD and may offer new avenues for developing effective AD treatments.