Search and development of antidiabetic agents based on anti-AGEs activity

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: MATSUDA Hisashi 京都薬科大学, 薬学部, 教授 (40288593)
• Co-Investigator(Kenkyū-buntansha): 中村 誠宏 京都薬科大学, 薬学部, 准教授 (20411035)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 終末糖化産物 / PC12細胞 / 神経突起 / アルドース還元酵素 / 指甲花 / オトメアゼナ / キンモクセイ / アマチャ

Outline of Final Research Achievements

In this study, we examined the inhibitory effects of the extracts of medicinal plants and their constituents on production of advanced glycation end-products (AGEs) and the AGEs-induced cell disorder using cultured cells. As a result, the extracts of flower of Lawsonia inermis improved the decrease in development of neurites of PC12 cells by a glycated-bovine serum albumin (Glycated-BSA), and searching for the active constituents using bioassay together, and flavonoids such as (±)-eriodictyol are found as active constituents. The flower extract of Osmanthus fragrans var. aurantiacus inhibited production of AGEs, and 10-acetoxyligstroside was found to be an active constituent. In addition, we found that the extract of whole plants of Bacopa monniera and its constituents plantainoside B et al. inhibited production of AGEs and aldose reductase (AR). The processed leaves of Hydrangea macrophylla var. thunbergii and its constituents, thunberginols A, B, and F, also inhibited the AR.

Free Research Field

薬用資源学，生薬学

Academic Significance and Societal Importance of the Research Achievements

糖尿病治療には血糖降下薬など優れた医薬品が開発されているが，合併症の治療薬としてはアルドース還元酵素阻害剤のみしか開発に成功していない。私たちははこれまでに糖尿病に有効と伝承されてきた天然薬物を素材として探索を行ってきた結果，多様な終末糖化産物（AGEs）の生成抑制物質を明らかにしてきた。本研究においては，AGEs生成抑制物質のみならずAGEsによる神経細胞や血管内皮に対する機能障害を抑制する物質を見出し，糖尿病合併症における神経変性や血管内皮障害に有効な物質を探索し，新しい医薬シーズの探索を目指すことに意義がある。