Elucidation of the oxidative stress suppression mechanism in the neurovascular unit of polyphenolic metabolites

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K02377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 08030:Family and consumer sciences, and culture and living-related
• Research Institution: The University of Nagano
• Principal Investigator: Ishii Yoko 長野県立大学, 健康発達学部, 教授 (00361949)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 酸化ストレス / 神経細胞 / ポリフェノール

Outline of Final Research Achievements

The purpose of this study was to elucidate that polyphenol metabolites with high bioavailability in the brain protect neurons from oxidative stress via cell-cell interaction in neurovascular units. The effect of polyphenol metabolites on oxidative stress-induced cell death was investigated using a two-layer co-culture model of cultured cell lines of neurons and astrocytes or vascular endothelial cells. Gallic acid and Urolithin-A maintained neuronal viability and increased SOD activity through attenuation of ROS levels. These antioxidant stress effects were increased by co-cultured astrocytes and neurons rather than monolayer neurons. The Nrf2/ARE signal was enhanced by Gallic acid and Urolithin-A in co-cultured astrocytes, suggesting that the signal might be one of the intercellular factors. Regarding the polyphenol metabolites examined in this study, the cell-cell interaction between neurons and vascular endothelial cells in co-culture was unclear.

Free Research Field

食生活学

Academic Significance and Societal Importance of the Research Achievements

認知症の原因の多くを占めるアルツハイマー病では、脳内で発生する酸化ストレスや炎症が病態を悪化させることが知られている。ポリフェノール代謝産物は抗酸化作用から神経保護効果が期待されているが、神経保護のメカニズムの詳細は明らかにされていない。本研究は，脳内で高いbioavailabilityと検出性を備えたポリフェノール代謝産物であるGallic acidとUrolithin-Aが神経保護作用を示すことと、その作用は星状膠細胞との細胞間相互作用を介して発揮されることを培養細胞系において明らかにした。同分子の前駆体を含む茶やベリー類等は酸化ストレス性神経障害を低減させる可能性が示唆された。