FABP4 as a Key Target of Hederagenin in Ischemic Stroke: A Study Based on Network Pharmacology and Experimental...

Ischemic Stroke (IS) shows high rates of mortality and disability, with a rising incidence. Persicae Semen (TaoRen), a traditional Chinese medicine, is known to promote blood circulation and resolve stasis. This study aimed to screen its active components and identify their anti-IS targets.

Transcriptome and single-cell data of IS were obtained from the GEO database. TaoRen's active components and targets were predicted using TCMSP and SwissTargetPrediction. Differentially Expressed Genes (DEGs) were screened using the limma package. The predicted target genes of TaoRen were intersected with these IS-related DEGs to identify the candidate key therapeutic targets. Subsequently, a regulatory network was constructed and visualized using Cytoscape. Functional enrichment analysis was performed using GSEA to explore the biological pathways involved. Molecular docking was performed using AutoDockTools to validate the binding affinity between the active components and the core targets. Finally, single-cell transcriptomic data were analyzed using the Seurat package. RT-qPCR, CCK-8, flow cytometry, and commercial kits were used to identify the protective effect of Hederagenin (HE) against OGD/R damage on PC12 cells.

Four active ingredients (α1-sitosterol, Hederagenin (HE),β-sitosterol, campesterol) of TaoRen were identified. FABP4, which was highly expressed in IS samples, was identified as a key target involved in ROS and mitochondrial pathways. Molecular docking confirmed strong binding between FABP4 and HE. Single-cell analysis showed that FABP4 is predominantly expressed in vascular smooth muscle and brain endothelial cells. HE treatment downregulated FABP4 expression, protected PC12 viability, and suppressed apoptosis and oxidative stress.

This study identified HE,β-sitosterol, and campesterol as key components of TaoRen that target FABP4, demonstrating neuroprotection against IS through oxidative stress and mitochondrial pathways. However, limitations such as insufficient validation and potential challenges to cross-species translatability should be addressed.

This study identified four bioactive compounds from TaoRen and verified FABP4 as a potential target for IS, contributing to the development of TaoRen-derived therapeutic agents for IS treatment.