Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats

Abstract In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extrac...

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Autores principales:	Ying Huang, Xiangping Liao, Huaiwei Wang, Jianghong Luo, Shanquan Zhong, Ziliang Zhang, Fang zhang, Jianping Chen, Fuhua Xie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02900d40dc404f95aade2c8cffe0e75e
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spelling	oai:doaj.org-article:02900d40dc404f95aade2c8cffe0e75e2021-12-02T13:44:14ZEffects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats10.1038/s41598-021-88206-72045-2322https://doaj.org/article/02900d40dc404f95aade2c8cffe0e75e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88206-7https://doaj.org/toc/2045-2322Abstract In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.Ying HuangXiangping LiaoHuaiwei WangJianghong LuoShanquan ZhongZiliang ZhangFang zhangJianping ChenFuhua XieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Huang Xiangping Liao Huaiwei Wang Jianghong Luo Shanquan Zhong Ziliang Zhang Fang zhang Jianping Chen Fuhua Xie Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
description	Abstract In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.
format	article
author	Ying Huang Xiangping Liao Huaiwei Wang Jianghong Luo Shanquan Zhong Ziliang Zhang Fang zhang Jianping Chen Fuhua Xie
author_facet	Ying Huang Xiangping Liao Huaiwei Wang Jianghong Luo Shanquan Zhong Ziliang Zhang Fang zhang Jianping Chen Fuhua Xie
author_sort	Ying Huang
title	Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
title_short	Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
title_full	Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
title_fullStr	Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
title_full_unstemmed	Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
title_sort	effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/02900d40dc404f95aade2c8cffe0e75e
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Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats

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