Kaixin San in treating vascular dementia via regulating the Bcl-2/Beclin-1/LC3A/B signaling pathway via animal experiments and network pharmacology analysis

Background: Kaixin San (KXS), a traditional Chinese herbal formula, is used to treat vascular dementia (VaD), but its active ingredients and mechanisms remain unclear. This study combined animal experiments with network pharmacology to explore how KXS modulates the Bcl-2/Beclin-1/LC3A/B pathway in VaD treatment. Results: LC‒MS/MS identified 164 active ingredients in the KXS ethanol extract. In 2-vessel occlusion model rats, KXS significantly improved learning and memory (p < 0.05 or p < 0.01) and reduced hippocampal CA1 neuronal damage. Western blotting showed KXS upregulated Bcl-2/Bcl-XL and downregulated Beclin-1, LC3A/B, and Bax (p < 0.05). Immunofluorescence confirmed increased Bcl-2 and decreased Beclin-1 expression. Network pharmacology predicted 73 targets and 174 pathways, with TNF, AKT1, IL-1β, PTGS2, and ESR1 as key targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis linked these targets to cancer, atherosclerosis, and AGE-RAGE signaling pathways. Conclusions: KXS alleviates VaD by modulating autophagy and apoptosis via Bcl-2/Beclin-1/LC3A/B, with multi-target, multi-pathway effects. These findings support further investigation of KXS as a potential therapy for VaD.How to cite: Li M, Lu Y, Li Y, et al. Kaixin San in treating vascular dementia via regulating the Bcl-2/Beclin-1/LC3A/B signaling pathway via animal experiments and network pharmacology analysis. Electron J Biotechnol 2025;78. https://doi.org/10.1016/j.ejbt.2025.08.001.