Trial of Therapeutic Application of Hinokitiol to Inflammatory Bowel Disease Based on Corrective Effects of Iron Dynamics Abnormalities

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20886
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Kitamoto Hiroki 京都大学, 医学研究科, 医員 (80967901)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 炎症性腸疾患 / 鉄 / マクロファージ / ヒノキチオール

Outline of Final Research Achievements

A trend toward decreased intracellular iron and inflammation-inducing capacity was observed when mouse macrophage cell lines were treated with Hinokitiol during LPS stimulation.
RNA-seq was also performed to elucidate the molecular mechanism by which the inflammatory potential of macrophages is reduced when intracellular iron is lowered, and changes in genes involved in intracellular metabolism such as glucose metabolism and oxidative phosphorylation were identified in the iron-chelated group. We focused on the AMPK pathway, which is upregulated in the iron-chelate group, and found that the inflammatory potential of the iron-chelate group was partially restored by the use of an AMPK inhibitor.

Free Research Field

炎症性腸疾患

Academic Significance and Societal Importance of the Research Achievements

今回Hinokitiolを用いた研究はin vitroでの検討までしか出来なかったが、マウスのマクロファージ細胞株でHinokitiolが抗炎症作用を発揮する可能性を確認できた。またマクロファージの細胞内鉄の多寡が糖代謝に影響を及ぼして炎症惹起能を調節しているメカニズムが示唆され、IBD治療の新たな切り口として開発できる可能性が示唆された。
今後、IBDモデルマウスを用いたin vivoの実験系においても、ヒノキチオールの抗炎症作用と安全性が検証出来れば、将来的に実臨床への応用の可能性も期待される。