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Rubus fruticosus leaf extract inhibits vascular dementia-induced memory impairment and neuronal loss by attenuating neuroinflammation

  • Nak Song Sung (Department of General Surgery, Konyang University Hospital) ;
  • Sun Ho Uhm (Research Institute, Healinols Inc.) ;
  • Hyun Bae Kang (Research Institute, Healinols Inc.) ;
  • Nam Seob Lee (Department of Anatomy, College of Medicine, Konyang University) ;
  • Young-Gil Jeong (Department of Anatomy, College of Medicine, Konyang University) ;
  • Do Kyung Kim (Department of Anatomy, College of Medicine, Konyang University) ;
  • Nak-Yun Sung (Division of Natural Product Research, Korea Prime Pharmacy Co., Ltd.) ;
  • Dong-Sub Kim (Division of Natural Product Research, Korea Prime Pharmacy Co., Ltd.) ;
  • Young Choon Yoo (Department of Microbiology, College of Medicine, Konyang University) ;
  • Seung Yun Han (Department of Anatomy, College of Medicine, Konyang University)
  • Received : 2023.07.16
  • Accepted : 2023.07.25
  • Published : 2023.12.31

Abstract

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

Keywords

Acknowledgement

This work was supported by Konyang University Myunggok Research Fund (2018) and Basic Research Program funded by Ministry of Science and ICT (RS-2023-00251456).

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