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L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway.

Abstract：

:As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed extract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n-butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cerebral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n-butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyramidal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular dementia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n- butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.

journal_name

Neural Regen Res

journal_title

Neural regeneration research

authors

Huai Y,Dong Y,Xu J,Meng N,Song C,Li W,Lv P

doi

10.3969/j.issn.1673-5374.2013.19.001

subject

Has Abstract

pub_date

2013-07-05 00:00:00

pages

1733-42

issue

19

eissn

1673-5374

issn

1876-7958

pii

NRR-8-1733

journal_volume

8

pub_type

杂志文章

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