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

• 作者: Bei-ni Wang Cheng-biao Wu Zi-miao Chen Pei-pei Zheng Ya-qian Liu Jun Xiong Jing-yu Xu Pei-feng Li Abdullah Al Mamun Li-bing Ye Zhi-long Zheng Yan-qing Wu Jian Xiao Jian Wang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: Neuropharmacology
• 页码范围: 347-360
• 页数: 14页
• 语种: 英文

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·kg-1·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.