Get your full text copy in PDF
Bin Liu, Guoliang Liu, Yueyang Wang, Yuan Yao, Guanzhuo Wang, Xia Lei, Ning Zhang, Xiaohong Dong
(Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi, Heilongjiang, China (mainland))
Med Sci Monit 2019; 25:7813-7825
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-ß 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-1ß, IL-6, TNF-alpha, and Aß25-35 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-kappaBp65 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 Aß25-35. 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-kappaBp65 pathways.
CONCLUSIONS: BYHWD regulates Aß metabolism via the RAGE/LRP1 pathway, inhibits vascular endothelial inflammation induced by ICAM-1 and VCAM-1 via the NF-kappaBP65 pathway, and promotes morphological changes induced by Aß-induced brain microvascular endothelial cell damage.