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
  • 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: [email protected].
  • 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: [email protected].
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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