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| Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/β -Catenin Signaling |
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| KeyWord:Alzheimer disease, Chinese medicine, neuroprotective agent, apoptosis regulatory proteins, Fructus broussonetiae |
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| Abstract: |
| Objective: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). Methods: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aβ 25–35 in order to establish an in vitro model of AD. Results: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and β -catenin signaling. Similarly, FB up-regulated both AKT and β -catenin signaling in PC-12 cells pre-treated with Aβ 25–35, in which AKT positively regulated β -catenin signaling. Further study showed that AKT promoted β -catenin signaling via enhancing β -catenin (Ser552) phosphorylation. Moreover, AKT and β -catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/β -catenin signaling is a crucial mediator in FB promoted cell survival. Conclusions: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/β -catenin signaling. |
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