Effects of Rikkunshito on upstream therapy for atrial fibrillation through a ghrelin signaling

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Oita University
• Principal Investigator: Nakagawa Mikiko 大分大学, 医学部, 教授 (50244182)
• Co-Investigator(Kenkyū-buntansha): 安部 一太郎 大分大学, 医学部, 病院特任助教 (00747595)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 六君子湯 / グレリン / 心房細動 / 心房筋線維化 / 漢方薬

Outline of Final Research Achievements

Atrial fibrillation (AF) is a frequent arrhythmia that is associated with morbidity and mortality. Ghrelin is an acylated peptide hormone secreted by the stomach and includes stimulation of growth hormone secretion and inhibition of inflammation and apoptosis in the hearts. These observations led to a hypothesis that potentiation of ghrelin signaling can attenuate angiotensin II (AngII)-induced AF. Rikkunshito (RKT) is a traditional herbal medicine widely used in patients with gastrointestinal symptoms. It has been reported that RKT potentiates ghrelin signaling and exert anti-inflammatory and anti-fibrotic effects in several organs. This study tested the hypothesis that RKT can suppress AngII-induced inflammatory atrial fibrosis and ameliorate enhanced vulnerability to AF. Our results demonstrated that RKT suppresses atrial inflammatory fibrosis and enhances AF vulnerability in mice induced by continuous subcutaneous AngII infusion by potentiating the GHSR-Sirt1 pathway.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

心房細動は発生頻度の高い不整脈であり心原性脳梗塞の原因となるため、その予防法の開発は重要な課題である。消化管に働くペプチドホルモンのグレリンが、心臓においては心房の炎症や線維化を抑制し、心房細動の発症を抑制する可能性が示唆されている。漢方薬の六君子湯はグレリン分泌薬であり、胃薬として広く使用されている。本研究では、六君子湯に心房筋の線維化を抑制し、心房細動の発症を抑制する効果があることを世界で初めて立証した。六君子湯は心房細動の予防薬として、健康長寿を実現する手段の一つとなり得る可能性が示唆される。