Metabolic pathway and blood brain barrier permeability of anthocyanin component and its metabolites

Research Project

Project/Area Number	18K11113
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	Nigata University of Phermacy and Applied Life Sciences
Principal Investigator	MATSUMOTO HITOSHI 新潟薬科大学, 応用生命科学部, 教授 (00566292)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	Anthocyanin / blood brain barrier / nobiletin / equol / isoflavone / Kaempferol / anthocyanin / 4-Hydroxybenzoic acid / Protocatechuic acid / Blood Brain Barrier / アントシアニン / Phloroglucinol aldehyde / 血液脳関門 / 代謝物
Outline of Final Research Achievements	Cassis and strawberry anthocyanins (AC) were concentrated to prepare an extract powder of about 10% AC content. These extracts were administered to rats, and AC and its metabolites in blood, urine, and brain were quantitatively analyzed. AC and its metabolites were detected in urine, small amounts were detected in blood and brain, and it was confirmed that they were absorbed and transferred into the blood and excreted. Blood-brain barrier (BBB) permeability was evaluated with a BBB kit. As a result, AC and its metabolites did not permeate BBB, and Epigallocatechin was confirmed to permeate. Daidzein, Genistein, Equol, and Nobiletin showed high BBB permeability. Rutin, Fisetin, Resveratrol, and Curcumin showed low BBB permeability. Regarding AC, it does not permeate BBB, and the brain function improving effect of AC is not direct effect in brain by AC or metabolites, it is a secondary effect, for example, improving blood circulation.
Academic Significance and Societal Importance of the Research Achievements	ヒト臨床試験などでアントシアニン(AC)の摂取が、認知機能低下の抑制効果があることが報告されている。また、そのメカニズムとして、神経細胞培養系にACを添加して、機能性を評価するin vitro試験が報告されている。しかし、ACの血液脳関門(BBB)の透過性については評価されていなかった。そこで、食品由来のACをラットに経口摂取させ、脳中のACと代謝物量を測定し、極微量検出した。また、キットを用いて透過性を評価したが、いずれも透過しなかった。よって、脳で検出されるACは、脳血管に吸着していて、脳には到達していないと判断された。AVの認知機能改善効果は、血流改善等による二次的な効果と考えられた。