Development of natural products based on regulation of biological clock system

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Ishikawa Prefectural Nursing University (2020-2021); Aichi Gakuin University (2019)
• Principal Investigator: Hirai Takao 石川県立看護大学, 看護学部, 教授 (80389072)
• Co-Investigator(Kenkyū-buntansha): 中島 健一 愛知学院大学, 薬学部, 准教授 (70635135)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 時計遺伝子

Outline of Final Research Achievements

Recent studies indicated that circadian disruptions are associated with metabolic disorders. In this study, we aimed to identify natural products that modulate the transcriptional regulatory network of clock genes using crude herbal drugs frequently used for the preparation of Kampo prescriptions. First, we attempted to search for small molecules acting on ROR or Rev-erb based on the expression pattern of the BMAL1 promoter-driven luciferase gene. As a result, we found several crude drug extracts that decrease BMAL1 mRNA expression. In addition, analysis of the main active constituents of the extracts suggested that it may be involved in the regulation of cell differentiation in adipose progenitor. Furthermore, this study indicated that clock genes were involved in the expression of FGF21. Thus, these results may lead to the development of novel therapeutic agents based on chronopharmacology.

Free Research Field

分子薬理学

Academic Significance and Societal Importance of the Research Achievements

近年、生体時計は基本的生命現象だけでなく、病態解明や治療の標的として注目されている。本研究成果より、時計遺伝子の転写調節ネットワークを標的とする天然薬物の探索は肥満改善薬の創出に向けて有用である可能性が示唆された。また、時計遺伝子の転写調節ネットワークに作用する天然薬物の探索だけでなく、褐色脂肪細胞における時計遺伝子の新たな機能を見出した本研究成果は、時間薬理学に基づいた生活習慣病・老齢化疾患に対する新たな治療や予防法の開発、治療理論の構築に繋がると考えられる。