DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress

doi:10.1038/s41401-020-00583-3

科研成果详情

题名	DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress
作者	Wang, Bei-ni1,2; Wu, Cheng-biao 3; Chen, Zi-miao1; Zheng, Pei-pei 2; Liu, Ya-qian 2; Xiong, Jun 2; Xu, Jing-yu 4; Li, Pei-feng1; Mamun, Abdullah Al 2; Ye, Li-bing 2; Zheng, Zhi-long 2; Wu, Yan-qing 4; Xiao, Jian1,2; Wang, Jian1
发表日期	2021-03
发表期刊	ACTA PHARMACOLOGICA SINICA 影响因子和分区
语种	英语
原始文献类型	Article
关键词	diabetes-associated cognitive decline DL-3-n-butylphthalide cognitive function hippocampus BDNF oxidative stress neuroprotection
其他关键词	CHRONIC CEREBRAL HYPOPERFUSION ; NEUROLOGICAL DEFICITS ; TAU PHOSPHORYLATION ; NERVOUS-SYSTEM ; STEM-CELLS ; IMPAIRMENT ; MICE ; L-3-N-BUTYLPHTHALIDE ; ACTIVATION ; DISEASE
摘要	DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg center dot kg(-1)center dot d(-1)) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81801233, 81870842, 81801245, 81802238]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ18H090011, LGD21H070001]
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	1671-4083
EISSN	1745-7254
卷号	42 期号:3 页码:347-360
DOI	10.1038/s41401-020-00583-3
页数	14
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS记录号	WOS:000608661700002
收录类别	SCIE ; PUBMED ; SCOPUS ; CSCD
学科领域	医药、卫生
URL	查看原文
CSCD记录号	CSCD:6926861
PubMed ID	33462377
PMC记录号	PMC8027654
SCOPUSEID	2-s2.0-85099395511
ESI高被引论文	2022-05 ; 2023-01 ; 2023-03 ; 2023-05 ; 2023-07
通讯作者地址	[Xiao, Jian]Department of Hand Surgery and Peripheral Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China ; [Wang, Jian]Department of Hand Surgery and Peripheral Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China ; [Wu, Yan-qing]The Institute of Life Sciences,Engineering Laboratory of Zhejiang province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou University,Wenzhou,325035,China
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计	被引频次：30[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17890
专题	药学院（分析测试中心）附属第一医院研究生工作部（研究生院）其他_附属象山医院（象山县第一人民医院）其他_附属萧山医院（杭州市萧山区第一人民医院）
通讯作者	Wu, Yan-qing; Xiao, Jian; Wang, Jian
作者单位	1.Department of Hand Surgery and Peripheral Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325000,China; 3.Research Center,Affiliated Xiangshan Hospital,Wenzhou Medical University,Ningbo,315700,China; 4.The Institute of Life Sciences,Engineering Laboratory of Zhejiang province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou University,Wenzhou,325035,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Wang, Bei-ni,Wu, Cheng-biao,Chen, Zi-miao,et al. DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress[J]. ACTA PHARMACOLOGICA SINICA,2021,42(3):347-360.
APA	Wang, Bei-ni., Wu, Cheng-biao., Chen, Zi-miao., Zheng, Pei-pei., Liu, Ya-qian., ... & Wang, Jian. (2021). DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress. ACTA PHARMACOLOGICA SINICA, 42(3), 347-360.
MLA	Wang, Bei-ni,et al."DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress".ACTA PHARMACOLOGICA SINICA 42.3(2021):347-360.