Ding-zhi-xiao-wan attenuates Alzheimer's disease pathology and cognitive deficits in mouse model

Ding-zhi-xiao-wan (DZXW) is a classic prescription applied for the therapy of forgetfulness and dizziness. However, the mechanisms of DZXW in ameliorating cognition deficits in Alzheimer's disease (AD) have not been fully determined. To comprehensively illuminate the overall beneficial effects and the underlying molecular mechanisms of DZXW to AD.

An initial network pharmacology analysis was performed, including of construction of multiple networks and enrichment of gene ontology, and analysis of signal pathway. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms from network pharmacology.

39 active compounds in DZXW corresponding to 224 genes related to AD protection were found. The therapeutic mechanisms of DZXW to protect AD predicted from the network pharmacology were primarily related to the negative regulation of neuroinflammation and oxidative stress. Compared to AD model mice, DZXW-administeredmice explored new objects more often, demonstrated a significantly shorter escape latency, passed through the platform more frequently, and stayed in the platform quadrant longer. Furthermore, DZXW-administeredmice showed a markedly less burden of Aβ plaques, lower number of activated microglias in the mice brain, enhanced activity of superoxide dismutase (SOD) and glutathione (GSH), and lower level of malondialdehyde (MDA) in mice.

DZXW could be a therapeutic candidate for AD by inhibiting neuroinflammation and oxidative stress.