Study on the mechanism of acorus tatarinowii in the treatment of Alzheimer's disease based on network pharmacology, molecular docking and molecular dynamics simulation

Background Acorus tatarinowii is a traditional Chinese medicine with potential therapeutic value for Alzheimer’s disease (AD). However, the active components responsible for its efficacy and the underlying mechanisms remain to be fully elucidated. Methods This study integrated network pharmacology predictions with experimental validation, focusing on the mechanism of Tatarine A in treating AD. Results In vivo experiments showed that the aqueous extract of Acorus tatarinowii significantly improved cognitive function in AD mice. UPLC-MS/MS was used to analyze the aqueous extract of Acorus tatarinowii and the serum components of extract-administered mice.Using the TCMSP, BATMAN 2.0 and TCMBank database, total of 36 active components and 281 corresponding targets were identified from Acorus tatarinowii. Through protein–protein interaction network analysis, 30 core potential targets were identified, six of which had crystal structures suitable for molecular docking. The study also yielded 3519 Gene Ontology terms and 195 Kyoto Encyclopedia of Genes and Genomes pathways. Molecular dynamics simulations confirmed stable interactions between ALB and the Tatarine A ligand system. CCK-8 assay showed that Tatarine A dose-dependently attenuated Aβ1–42-induced BV2 cell viability inhibition. ELISA and ThT staining revealed that Tatarine A reduced inflammatory cytokines, oxidative stress markers, and Aβ1–42 in AD mice. Western blot confirmed that Tatarine A downregulated p-STAT3/STAT3, p-NF-κB/NF-κB ratio and upregulated BCL-2 and ALB. Cell viability assays demonstrated that STAT3 and NF-κB activation abolished the cytoprotective effect of Tatarine A in BV2 cells. Conclusion This study confirms that Tatarine A, a promising active component of Acorus tatarinowii, exhibits neuroprotective activity against AD. It acts via the STAT3/NF-κB/BCL-2 signaling pathway, with ALB requiring further validation as a candidate binding target.