Puerariae Radix Prevents Anxiety and Cognitive Deficits in Mice Under Oligomeric Aβ-Induced Stress

Abstract

To evaluate the therapeutic effects of Chinese herbal medicine (CHM) for Alzheimer's disease (AD), we evaluated five CHMs in oligomeric A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mn>5</mml:mn><mml:mo>-</mml:mo><mml:mn>3</mml:mn><mml:mn>5</mml:mn></mml:mrow></mml:msub></mml:math>-treated mouse primary hippocampal neuronal cultures. The aqueous extract from the root of <i>Pueraria lobata</i> (Puerariae Radix; PR) showed better neuroprotective effects than did the other four CHM aqueous extracts, including <i>Gardenia jasminoides</i>, <i>Eleutherococcus senticosus</i>, <i>Rhodiola rosea</i>, and <i>Panax,</i> in the primary culture treated with saline or oligomeric A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mn>5</mml:mn><mml:mo>-</mml:mo><mml:mn>3</mml:mn><mml:mn>5</mml:mn></mml:mrow></mml:msub></mml:math>. Furthermore, the neuroprotective effects of aqueous extract of PR were also better than its well-known active compound, puerarin, against the neurotoxicity of oligomeric A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mn>5</mml:mn><mml:mo>-</mml:mo><mml:mn>3</mml:mn><mml:mn>5</mml:mn></mml:mrow></mml:msub></mml:math> in a primary culture. For <i>in vivo</i> experiments, C57BL/6J male mice that received direct infusion of soluble oligomeric A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mn>5</mml:mn><mml:mo>-</mml:mo><mml:mn>3</mml:mn><mml:mn>5</mml:mn></mml:mrow></mml:msub></mml:math> 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 A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math> 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 A<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mn>5</mml:mn><mml:mo>-</mml:mo><mml:mn>3</mml:mn><mml:mn>5</mml:mn></mml:mrow></mml:msub></mml:math>. 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.