2. Academic Validation
  3. Neuroprotective effects of Aucubin against cerebral ischemia-reperfusion injury

Neuroprotective effects of Aucubin against cerebral ischemia-reperfusion injury

  • Int Immunopharmacol. 2024 Mar 10:129:111648. doi: 10.1016/j.intimp.2024.111648.
Ying Liang 1,  Liqiu Chen 1,  Jing Huang 1,  Zhen Lan 2,  Shengnan Xia 3,  Haiyan Yang 3,  Xinyu Bao 3,  Xi Yu 4,  Yingao Fan 4,  Yun Xu 5,  Xiaolei Zhu 6,  Jiali Jin 7
Affiliations

Affiliations

  • 1 Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • 2 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.
  • 3 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China; Nanjing Neurology Medical Center, Nanjing 210008, China.
  • 4 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • 5 Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China; Nanjing Neurology Medical Center, Nanjing 210008, China.
  • 6 Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China; Nanjing Neurology Medical Center, Nanjing 210008, China. Electronic address: zhuquelee@126.com.
  • 7 Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China; Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China; Nanjing Neurology Medical Center, Nanjing 210008, China. Electronic address: jjllily@126.com.
PMID: 38335656 DOI: 10.1016/j.intimp.2024.111648
Abstract

Aims: To study the role of Aucubin (AU) in cerebral ischemia-reperfusion injury and investigate the potential mechanisms.

Methods: For the in vitro experiment, primary microglia were cultured and stimulated by Lipopolysaccharides (LPS) and treated with AU. Male C57/BL6J mice were used and middle cerebral artery occlusion (MCAO) model was performed to induce cerebral ischemia-reperfusion injury. For the short-term effects, mice administrated with AU (40 mg/kg) for 3 days after MCAO were evaluated for the infarct volume and neurological deficits. The neuroinflammatory factors and microglia activation were determined by Real-Time PCR, western blot and immunofluorescence staining. For the long-term effects, MCAO mice were injected daily with AU (5 mg/kg or 10 mg/kg) for 28 days. Behavior tests were used to assess the neurological deficits of MCAO mice, and white matter integrity was determined by myelin basic protein (MBP) staining and black-gold staining.

Results: AU suppressed LPS-induced activation of microglia and pro-inflammatory cytokines release, and downregulated the NF-κB and MAPK pathways in primary microglia. In addition, AU attenuated ischemic injury and inhibited the neuro-inflammatory response in MCAO mice. Moreover, AU induced prolonged improvements in sensorimotor function and memory function following MCAO, and preserved white matter integrity in the long-term experiments.

Conclusions: AU protected against ischemic injury, which might be correlated with the downregulation of NF-κB and MAPK signaling pathways. Furthermore, AU alleviated cognitive impairment after stroke and restored white matter integrity. Our data indicated that AU might be a potential compound for the treatment of stroke and post-stroke cognitive impairment.

Keywords

Aucubin; MAPK pathway; NF‐κB pathway; Neuroinflammation; Post-stroke cognitive impairment.

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