<i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling
Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effe...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5259 |
| _version_ | 1797611294792089600 |
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| author | Wenshu Zhou Bingxi Lei Chao Yang Marta Silva Xingan Xing Hua Yu Jiahong Lu Wenhua Zheng |
| author_facet | Wenshu Zhou Bingxi Lei Chao Yang Marta Silva Xingan Xing Hua Yu Jiahong Lu Wenhua Zheng |
| author_sort | Wenshu Zhou |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of <i>Artemisia annua</i> (<i>A. annua</i>) extract on AD. Nine-month-old female 3xTg AD mice were treated with <i>A. annua</i> extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced Aβ accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, <i>A. annua</i> extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that <i>A. annua</i> extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with Aβ<sub>1–42</sub> at a concentration of 8 μM with or without different concentrations of <i>A. annua</i> extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that <i>A. annua</i> extract significantly reversed the Aβ<sub>1–42</sub>-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the <i>A. annua</i> extract. These findings suggest that <i>A. annua</i> extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:52Z |
| publishDate | 2023-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-36c6ef7c651e42dd85c54aac4593d3eb2023-11-17T11:31:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246525910.3390/ijms24065259<i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP SignalingWenshu Zhou0Bingxi Lei1Chao Yang2Marta Silva3Xingan Xing4Hua Yu5Jiahong Lu6Wenhua Zheng7Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaCenter of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaCenter of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaCenter of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaCenter of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaCenter of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaAlzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of <i>Artemisia annua</i> (<i>A. annua</i>) extract on AD. Nine-month-old female 3xTg AD mice were treated with <i>A. annua</i> extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced Aβ accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, <i>A. annua</i> extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that <i>A. annua</i> extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with Aβ<sub>1–42</sub> at a concentration of 8 μM with or without different concentrations of <i>A. annua</i> extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that <i>A. annua</i> extract significantly reversed the Aβ<sub>1–42</sub>-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the <i>A. annua</i> extract. These findings suggest that <i>A. annua</i> extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD.https://www.mdpi.com/1422-0067/24/6/5259Alzheimer’s disease<i>Artemisia annua</i>neuroprotective effectAD-type pathologiesYAP signaling pathway |
| spellingShingle | Wenshu Zhou Bingxi Lei Chao Yang Marta Silva Xingan Xing Hua Yu Jiahong Lu Wenhua Zheng <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling International Journal of Molecular Sciences Alzheimer’s disease <i>Artemisia annua</i> neuroprotective effect AD-type pathologies YAP signaling pathway |
| title | <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling |
| title_full | <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling |
| title_fullStr | <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling |
| title_full_unstemmed | <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling |
| title_short | <i>Artemisia annua</i> Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling |
| title_sort | i artemisia annua i extract improves the cognitive deficits and reverses the pathological changes of alzheimer s disease via regulating yap signaling |
| topic | Alzheimer’s disease <i>Artemisia annua</i> neuroprotective effect AD-type pathologies YAP signaling pathway |
| url | https://www.mdpi.com/1422-0067/24/6/5259 |
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