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Artemisia annua extracts improve the cognitive deficits and reverse the pathological changes of Alzheimer's disease via the Hippo pathway

Artemisia annua extracts improve the cognitive deficits and ...

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世界中医药学会联合会老年医学专业委员会2021年学术年...

作者： WenShu Zhou Yang Chao Marta Silva XinGan Xing YiTian Chen WenHua Zheng Center of Reproduction Development & Aging Faculty of Health SciencesUniversity of Macau Institute of Translation Medicine Faculty of Health Sciences University of Macau

Alzheimer’s disease(AD) is a chronic neurodegenerative disease characterized by cognitive deficits such as the loss of memory of recent events. The major pathological changes of AD are extracellular amyloid-β(Aβ) plaques and intracellular neurofibrillary tangles(NFTs) composed of hyperphosphorylated microtubule-associated tau protein and lot of neuronal death. So far, there is no effective drug for the treatment of AD and the search for new effective therapies has become the major focus. In this study, we describe the potential therapeutic effect on AD of a water solvable artemisia annua extract(Ex1) in vivo and in vitro. Our in vitro studies revealed that Ex1 significantly reversed Aβ1-42-induced increase of ROS levels, caspase-3 activity, and neuronal cell apoptosis. Western blot analysis showed that Ex1 alleviated Aβ1-42-induced inflammation and the phosphorylation of Tau. It also stimulated the activation of YAP/TAZ signaling pathway in PC12 cells in a time and concentration-dependent manner indicating the involvement of this pathway in the effect of Ex1. Consistent with this hypothesis, inhibition of the YAP/TAZ signaling pathway by its specific inhibitor or siRNA reduced the neuroprotective effect of the Ex1. More importantly, oral administration of the Ex1 to AD 3xtg mice significantly improved the cognitive deficits, reduced Aβ accumulation, hyper-tau-phosphorylation and the release of inflammatory factor and apoptosis in AD mice. Additionally, Ex1 promoted the survival and proliferation of neural progenitor cells(NPs), increased the expression of synaptic proteins and neuronal cell survival. The extracts also stimulated the activation of YAP/TAZ signaling pathway in 3xtg AD mice like it does in previous studies in PC12 cells. Taken together, these findings revealed that Ex1 is able to relief AD symptoms and to reverse the pathological changes of AD in vitro and in vivo via the activation of the YAP/TAZ pathway. Our findings also suggest that Ex1 may be a ne

关键词： Alzheimer’s disease Artemisia annua extracts Neuronal apoptosis AD-type pathologies 3xtg mice

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