Investigation of cytoprotective triggering mechanism of flavonoids targeting stress sensing mechanisms

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Nagoya University
• Principal Investigator: Matsushima Miyoko 名古屋大学, 医学系研究科(保健), 講師 (10509665)
• Co-Investigator(Kenkyū-buntansha): 川部 勤 名古屋大学, 医学系研究科(保健), 教授 (20378219)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: フラボノイド / Nrf2 / オートファジー

Outline of Final Research Achievements

Flavonoids exhibit beneficial effects, and one such flavonoid, quercetin, exerts cytoprotective effects via HO-1 induced by Nrf2 activation. In the present study, we showed that quercetin-induced HO-1 was involved in the regulation of autophagy. Quercetin induced the conversion of LC3-I to LC3-II while also inducing p62 expression and phosphorylation at serine residue 351. These results suggest that quercetin would induce selective autophagy, and quercetin-induced p62 might create a positive feedback loop in Keap1-Nrf2 system. Moreover, HO-1 deletion enhanced the expression levels of p62 induced by quercetin, suggesting that HO-1 might negatively regulate p62 expression. In summary, quercetin induced selective autophagy, and HO-1 induced by quercetin negatively regulated the expression of p62. These results suggested that selective autophagy induced by quercetin might exert cytoprotective effects under regulation of HO-1 activity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ストレスは老化、炎症性疾患、アレルギー性疾患などさまざまな疾患の病態形成に関与し、ストレスによって誘導される生体防御機構がこれら疾患の制御の基盤となっている。フラボノイドは野菜等から摂取できるため、健康状態や疾患感受性に合わせたフラボノイドを含む食事指導を行うことで、より安全にかつ効果的にさまざまな疾患の発症を予防・軽減できる。本研究でフラボノイドがいかにストレスセンシング機構を作動させ、対応する生体防御機構を誘導するかを評価することにより、生体防御の強化やアンチエイジングに貢献し、これからの超高齢社会にも低コストで十分に対応できる対策を構築できる可能性があると考える。