Dl-3-n-butylphthalide attenuates cerebral ischemia/reperfusion injury in mice through AMPK-mediated mitochondrial fusion

被引:4
|
作者
Zhu, Ting [1 ]
Dong, Shanshan [1 ,2 ]
Qin, Na [1 ]
Liu, Rujuan [1 ,2 ]
Shi, Liuliu [1 ,3 ]
Wan, Qi [1 ]
机构
[1] Qingdao Univ, Inst Neuroregenerat & Neurorehabil, Sch Basic Med, Dept Pathophysiol, Qingdao, Peoples R China
[2] Qingdao Univ, Dept Rehabil Med, Affiliated Hosp, Qingdao, Peoples R China
[3] Qingdao Univ, Dept Neurosurg, Affiliated Hosp, Qingdao, Peoples R China
基金
中国国家自然科学基金;
关键词
ischemic stroke; Dl-3-n-butylphthalide; mitochondrial fusion; AMPK; Mfn1; NLRP3; INFLAMMASOME; FISSION; NBP;
D O I
10.3389/fphar.2024.1357953
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: NBP is a compound isolated from celery seeds, which was approved by the National Medical Products Administration in 2002 for clinical treatment of ischemic stroke. However, in brain ischemia/reperfusion (I/R) injury, the related research on mitochondrial dynamics and its mechanism of action of NBP still need to be further studied. The aim of this study was to assess NBP on cerebral pathology in ischemic stroke in vivo, with a specific focus on the molecular mechanisms of how NBP promotes mitochondrial fusion.Methods: Male C57BL/6 mice were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Pre-ischemia, NBP was administered through intraperitoneal (i.p.) injection for 7 days.Results: Our findings demonstrated that NBP effectively reduced infarct volume, improved neurological dysfunction, enhanced cerebral blood flow, and promoted mitochondrial fusion in mice subjected to MCAO/R. More importantly, the pro-fusion effects of NBP were found to be linked to the activation of AMPK/Mfn1 pathway, and with the activation of neurological function, which was partially eliminated by inhibitors of AMPK.Discussion: Our results revealed that NBP is a novel mitochondrial fusion promoter in protecting against ischemic stroke through the AMPK-mediated Mfn1. These findings contribute to the understanding of novel mechanisms involved in the protection of neurological function following NBP treatment for ischemic stroke.
引用
收藏
页数:10
相关论文
共 50 条
  • [1] Dl-3-n-butylphthalide pretreatment attenuates renal ischemia/reperfusion injury
    Dong, Yang
    Yin, Jianyong
    Chen, Teng
    Wen, Jiejun
    Zhang, Qunzi
    Li, Xiaomei
    Lin, Wenjun
    Liu, Feng
    Fan, Ying
    Wang, Niansong
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2021, 557 : 166 - 173
  • [2] DL-3-n-butylphthalide Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting Mitochondrial Omi/HtrA2-Mediated Apoptosis
    Huang, Shuo
    He, Qianyan
    Sun, Xin
    Qu, Yang
    Abuduxukuer, Reziya
    Ren, Jiaxin
    Zhang, Kejia
    Yang, Yi
    Guo, Zhen-Ni
    [J]. CURRENT NEUROVASCULAR RESEARCH, 2023, 20 (01) : 101 - 111
  • [3] Effect of Dl-3-n-butylphthalide on mitochondrial Cox7c in models of cerebral ischemia/reperfusion injury
    Jia, Jingjing
    Deng, Jianwen
    Jin, Haiqiang
    Yang, Jie
    Nan, Ding
    Yu, Zemou
    Yu, Weiwei
    Shen, Zhiyuan
    Lu, Yuxuan
    Liu, Ran
    Wang, Zhaoxia
    Qu, Xiaozhong
    Qiu, Dong
    Yang, Zhenzhong
    Huang, Yining
    [J]. FRONTIERS IN PHARMACOLOGY, 2023, 14
  • [4] Dl-3-N-butylphthalide attenuates ischemic reperfusion injury by improving the function of cerebral artery and circulation
    Qin, Chuan
    Zhou, Panting
    Wang, Liping
    Mamtilahun, Muyassar
    Li, Wanlu
    Zhang, Zhijun
    Yang, Guo-Yuan
    Wang, Yongting
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2019, 39 (10): : 2011 - 2021
  • [5] Metformin protects against retinal ischemia/reperfusion injury through AMPK-mediated mitochondrial fusion
    Zhang, Kun
    Wang, Tao
    Sun, Gui-Feng
    Xiao, Jin-Xing
    Jiang, Li-Ping
    Tou, Fang-Fang
    Qu, Xin-Hui
    Han, Xiao-Jian
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2023, 205 : 47 - 61
  • [6] dl-3-n-butylphthalide attenuates reperfusion-induced bloodbrain barrier damage after focal cerebral ischemia in rats
    Chong, ZZ
    Feng, YP
    [J]. ACTA PHARMACOLOGICA SINICA, 1999, 20 (08): : 696 - 700
  • [7] Potential Protective Effect of Dl-3-n-butylphthalide on Chronic Cerebral Ischemia Brain Injury
    Zhao, Fangfang
    Luo, Yumin
    [J]. CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2022, 21 (09) : 734 - 737
  • [8] Dl-3-n-butylphthalide Attenuates Spinal Cord Injury via Regulation of MMPs and Junction Proteins in Mice
    Binbin Zheng
    Yanjun Jin
    Shuang Mi
    Wei Xu
    Xiangdong Yang
    Zhenghua Hong
    Zhangfu Wang
    [J]. Neurochemical Research, 2021, 46 : 2297 - 2306
  • [9] Dl-3-n-butylphthalide Attenuates Spinal Cord Injury via Regulation of MMPs and Junction Proteins in Mice
    Zheng, Binbin
    Jin, Yanjun
    Mi, Shuang
    Xu, Wei
    Yang, Xiangdong
    Hong, Zhenghua
    Wang, Zhangfu
    [J]. NEUROCHEMICAL RESEARCH, 2021, 46 (09) : 2297 - 2306
  • [10] Inhibiting of GRASP65 Phosphorylation by DL-3-N-Butylphthalide Protects against Cerebral Ischemia-Reperfusion Injury via ERK Signaling
    Zhu, Bei-lei
    Xie, Chen-long
    Hu, Ning-ning
    Zhu, Xin-bo
    Liu, Chun-feng
    [J]. BEHAVIOURAL NEUROLOGY, 2018, 2018