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

다국어 초록 (Multilingual Abstract)

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinf lammation. Polyphenol-rich natural plants, which possess anti-inf lammatory activities, have attractedscientific 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 treatedwith vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with mediumdose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral commoncarotid 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 neuroinf lammation were quantified intheir hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, andmicroglial 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 ofproinf lammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-inducedrelease of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest thatRFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to theattenuation of microglial activation.