To evaluate the therapeutic effects of Chinese herbal medicine (CHM) for Alzheimer's disease (AD), we evaluated five CHMs in oligomeric Aβ25-35-treated mouse primary hippocampal neuronal cultures. The aqueous extract from the root of Pueraria lobata (Puerariae Radix; PR) showed better neuroprotective effects than did the other four CHM aqueous extracts, including Gardenia jasminoides, Eleutherococcus senticosus, Rhodiola rosea, and Panax, in the primary culture treated with saline or oligomeric Aβ25-35. Furthermore, the neuroprotective effects of aqueous extract of PR were also better than its well-known active compound, puerarin, against the neurotoxicity of oligomeric Aβ25-35 in a primary culture. For in vivo experiments, C57BL/6J male mice that received direct infusion of soluble oligomeric Aβ25-35 into the bilateral hippocampal CA1 subregion were used as an alternative AD mouse model. The effects and molecular mechanisms of chronic systemic administration of PR aqueous extract were evaluated in the alternative AD model. PR aqueous extract prevented anxiety and cognitive impairment in mice associated with a decrease in the levels of Aβ deposition, tau protein phosphorylation, inflammation, loss of noradrenergic, and serotonergic neurons and an increase in the levels of synaptophysin and insulin degrading enzyme (IDE) against the toxicity of oligomeric Aβ25-35. Furthermore, no obvious damage to the liver and kidney was detected after chronic systemic administration of PR aqueous extract. Therefore, using PR could be a safer, more effective therapeutic strategy than using its active compound puerarin to prevent both cognitive and noncognitive dysfunction and related pathological features of AD.

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