title: 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.
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Huai
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Meng
authors.affiliation: Electron Microscope Center, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China ; Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Lv
keywords: 3-n-butylphthalide; Akt; Morris water maze; brain injury; cognitive function; dementia; grants-supported paper; hippocampus; ischemia/reperfusion; learning; memory; neural regeneration; neuroregeneration; phosphorylated Akt