Artemisia Annua Extracts Improve the Cognitive Deficits and Reverse the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Abstract Background: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by a progressive loss of memory and cognitive functions, language disorders, functional and behavioral alterations. The neurotoxicity is associated with the aggregation of β-amyloid (Aβ) plaques and the downstream pathologies events such as Tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysregulation play critical roles in the development of AD. With no effective treatment available for the prevention and treatment of AD, the search for new therapies has become the focus of many researchers.Methods: Artemisia annua extracts were extracted and a water-soluble artemisia annua extract (Ex1) was used in treatment for 3xTg AD mice via oral administration. Cognitive functional recovery, Aβ accumulation, hyper-tau-phosphorylation, and the release of inflammatory factors and apoptosis were assessed three months after the treatment. In vitro, PC12 cells were incubated with 8 μM Aβ1-42 with or without Ex1 at different concentrations for 24h. ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis, inflammation, and the phosphorylation of Tau, as well as involvement in the signaling pathway, were assessed by using biological technology. Results: Oral administration of Ex1 to AD 3xTg mice significantly improved the cognitive deficits, reduced Aβ accumulation, hyper-tau-phosphorylation, and the release of inflammatory factors and apoptosis. Ex1 promoted the survival and proliferation of neural progenitor cells (NPS), increased the expression of synaptic proteins and neuronal cell survival. Similarly, Ex1 significantly reversed the Aβ1-42-induced increase of ROS levels, caspase-3 activity, neuronal cell apoptosis, inflammation, and the phosphorylation of tau in vitro.Conclusions: These findings suggest that a water-soluble artemisia annua extract (Ex1) may be a new multi-target anti-AD drug with potential use in the prevention and treatment of Alzheimer’s disease.