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.