2022 Fiscal Year Final Research Report
Close relationship between pharmacological effects of Kampo medicines and aquaporin
| Project/Area Number |
20K07795
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | アクアポリン / 五苓散 / 炎症 / 止瀉作用 / 細胞内局在 |
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| Outline of Final Research Achievements |
Aquaporins (AQPs), water channels have been suggested as target molecules for some herbal medicines. In this study, we investigated the biological regulation of new functions of AQPs and their subcellular localization.In addition, we also examined effects of Kampo medicines on functions and expression of AQPs. First, we found that pulmonary epithelial AQP5 enhances the response to innate immune system cytokines, such as TNF-alpha, whereas it suppresses the response to Th2 cytokine responses. We have also defined the importance of C-terminal region of AQP5 and the interaction between AQP5 and ezrin for translocation of AQP5 to plasma membrane. In addition, we have found that the anti-diarrhea effect of Goreisan is through the increased expression of AQP3 in intestinal epithelial cells. In contrast, Goreisan inhibits AQP4, a brain-type AQP, mediated potentiation of inflammatory responses, resulting in a brain-selective anti-inflammatory effect.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
水チャネルのアクアポリン（AQP）類は，従来，外分泌機能や利尿など，体内の水分代謝の調節のための標的としての重要性が知られていた．しかし，本研究によって炎症応答など，水の移動とは無関係に生じる反応を調節し得ること，さらにその調節はAQPのアイソフォームによって異なることが判明した．さらに，五苓散をはじめとする漢方薬は，このAQP類による新機能を抑制することで，水分代謝調節と同時に抗炎症など，多彩な薬理作用を発揮し得ることが示唆された．本研究の成果は創薬標的としてのAQP類の新たな価値を示すとともに，これを利用した漢方薬の有用性を示すものである．
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