Abstract

BACKGROUND: The aim of this study was to investigate the protective mechanism of neurovascular unit of Buyang Huanwu decoction (BYHWD) in an Alzheimer’s disease (AD) cell model via RAGE/LRP1 pathway and find a reliable target for Alzheimer’s disease treatment.

MATERIAL AND METHODS: Rat brain microvessel endothelial cells (BMECs) were cultured in 10% FBS and 1% penicillin/streptomycin. The AD model was established by administration of 24 μmol/L amyloid-β peptides 25~35. Different concentrations of BYHWD (0.1 mg/mL, 1 mg/mL, and 10 mg/mL) were added as the drug intervention. The morphology of the cells was observed by light microscopy and the ultrastructure of the cells was observed by microscopy. The inflammatory factors IL-1β, IL-6, TNF-α, and Aβ25–35 were detected by ELISA. Flow cytometry was used to assess the apoptosis rate. The expressions of RAGE, LRP1, ICAM-1, VCAM-1, Apo J, Apo E, and NF-κBp65 were detected by Western blotting.

RESULTS: The structure of cells in BYHWDM and BYHWDH gradually recovered with increasing dose. BYHWD decreased the apoptotic rate of BMECs induced by Aβ25–35. The cells treated with different concentrations of BYHWD had significant difference in terms of anti-apoptotic effect. The therapeutic effect of BYHWD on AD was via the RAGE/LRP1 and NF-κBp65 pathways.

CONCLUSIONS: BYHWD regulates Aβ metabolism via the RAGE/LRP1 pathway, inhibits vascular endothelial inflammation induced by ICAM-1 and VCAM-1 via the NF-κBP65 pathway, and promotes morphological changes induced by Aβ-induced brain microvascular endothelial cell damage.

Keywords: Alzheimer Disease, endothelial cells, Microvascular Decompression Surgery, Amyloid beta-Peptides, Apoptosis, Brain, Cell Proliferation, Drugs, Chinese Herbal, Inflammation, LDL-Receptor Related Protein-Associated Protein, Models, Biological, primary cell culture, Rats, Receptor for Advanced Glycation End Products, Signal Transduction