DL-3-n-butylphthalide (NBP) alleviates poststroke cognitive impairment (PSCI) by suppressing neuroinflammation and oxidative stress

Hui Zhang; Laifa Wang; Yongping Yang; Chuanhai Cai; Xueqin Wang; Ling Deng; Binsheng He; Wenhu Zhou; Yanhui Cui

doi:10.3389/fphar.2022.987293

DL-3-n-butylphthalide (NBP) alleviates poststroke cognitive impairment (PSCI) by suppressing neuroinflammation and oxidative stress

Front Pharmacol. 2023 Jan 11:13:987293. doi: 10.3389/fphar.2022.987293. eCollection 2022.

Authors

Hui Zhang¹, Laifa Wang¹, Yongping Yang¹, Chuanhai Cai¹, Xueqin Wang¹, Ling Deng¹, Binsheng He^{1

2}, Wenhu Zhou^{1

2

3}, Yanhui Cui¹

Affiliations

¹ Neuroscience and Behavioral Research Center, Academician Workstation, Changsha Medical University, Changsha, China.
² Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China.
³ Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.

Abstract

Currently, the recovery of cognitive function has become an essential part of stroke rehabilitation. DL-3-n-butylphthalide (NBP) is a neuroprotective reagent and has been used in stroke treatment. Clinical studies have confirmed that NBP can achieve better cognitive outcomes in ischemic stroke patients than in healthy controls. In this study, we aimed to investigate the influences of NBP on cognitive function in an ischemic reperfusion (I/R) rat model. Our results showed that NBP profoundly decreased neurological scores, reduced cerebral infarct areas and enhanced cerebral blood flow (CBF). NBP potently alleviated poststroke cognitive impairment (PSCI) including depression-like behavior and learning, memory and social cognition impairments, in I/R rats. NBP distinctly suppressed the activation of microglia and astrocytes and improved neuron viability in the ischemic brain. NBP inhibited the expression of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), by targeting the nuclear factor kappa B/inducible nitric oxide synthase (NF-κB/iNOS) pathway and decreased cerebral oxidative stress factors, including reactive oxygen species (ROS) and malondialdehyde (MDA), by targeting the kelch like ECH associated protein 1/nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) pathway in the ischemic brain. The current study revealed that NBP treatment improved neurological function and ameliorated cognitive impairment in I/R rats, possibly by synergistically suppressing inflammation and oxidative stress.

Keywords: Dl-3-n-butylphthalide; acute ischemic stroke; inflammation; neuroprotectants; stress oxidation.

Grants and funding

This work was supported by the Research Foundation of Education Bureau of Hunan Province (Program No. 22C0673, 19B069, 19C0197, 19C0220), the Natural Science Foundation of Hunan Province (Program No. 2021JJ40644), the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi Wuzhou Medical College (Program No. 2021KY 1943, 2021KY 1947, 2021KY 1945), and the Hunan College Students Innovation and Entrepreneurship Training Program “The role of voltioxetine in posttraumatic stress disorder” to YY. The Natural Science Foundation of Changsha, China (kq2014117).