2022 Fiscal Year Final Research Report

Large metabolic nexus of the concept of renal deficiency as seen from Klotho

Research Project

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Project/Area Number	20K07852
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 52010:General internal medicine-related
Research Institution	Kagoshima University
Principal Investigator	Oyama Yoko 鹿児島大学, 医歯学総合研究科, 特任助教 (20583470)
Co-Investigator(Kenkyū-buntansha)	丸山征郎鹿児島大学, 医歯学総合研究科, 特任教授 (20082282) 山口宗一鹿児島大学, 医歯学域医学系, 准教授 (20325814) 橋口照人鹿児島大学, 医歯学域医学系, 教授 (70250917)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	老化 / 炎症 / 漢方薬 / 五苓散
Outline of Final Research Achievements	Inflammaging = inflammation + aging, a new pathology in which endogenous inflammation accelerates the aging process, has become evident. Based on the idea that "aging is a part of inflammation," we investigated the anti-aging effects of a Chinese herbal medicine, Goreisan, and a metabolite of a component of a crude drug Polygala Root, Component A. The results showed that administration of Goreisan and Component A to a renal failure animal model improved renal function and fibrosis, and many of them showed synergistic effects. The mechanism was that Goreisan has an anti-inflammatory effect and Component A has a broad cytoprotective effect including anti-inflammatory and antioxidant effects by activating AMPK, resulting in improvement of renal function and tubular damage. In addition to their anti-inflammatory effects, Goreisan and Component A significantly lowered phosphorus, an accelerator of aging, confirming their anti-inflammaging effects.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	今回の研究から、五苓散や遠志が含有する成分の代謝物：成分Aは腎不全モデルにおいて、血中リンおよび炎症性サイトカインMCP-1の有意な低下を示したことから、漢方薬がInflammaging制御によるエイジングコントローラーとなり得る可能性が示唆された。さらに、尿細管障害や腎機能の有意な改善、腎組織線維化の軽減といった実質的な機能改善を示したことから、これら薬剤が、現在治療法が限られている腎不全の治療薬となる可能性もあり、加えて五苓散と成分Ａの同時投与による相乗効果は、新たな漢方創薬の観点からも、今後さらなる発展が期待できるものと考えられる。