Experimental assessment of preventive effects of kampo medicines against metabolic syndromes through the modification of intestinal bile acid metabolism
Project/Area Number |
18K07441
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52010:General internal medicine-related
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Research Institution | University of Toyama |
Principal Investigator |
Watanabe Shiro 富山大学, 学術研究部薬学・和漢系, 准教授 (00222406)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 疎水性 / farnesoid X receoptor / デオキシコール酸 / ムリコール酸 / 腸内細菌 / 2次胆汁酸 / 糞便脂質排泄 / 腸管吸収 / 胆汁酸 / 16sRNA遺伝子 / 飽和脂肪酸 / FXR / TGR5 / 16s rRNA / リトコール酸 / farnesoid X 受容体 / FGF15/19 / glucagon-like peptide-1 |
Outline of Final Research Achievements |
The administration of Goreisan elevated the levels of secondary bile acids in the feces of mice. However, the assessments for the intestinal bacteria and their gene analysis were not successful to confirm the activation of bacterial synthesis of secondary bile acids by Goreisan. The changes in fecal bile acids by Goreisan were not associated with the changes in the levels of gene transcripts regulated by bile acid receptor activation in the colon. The administration of Boiogito increased the levels of deoxycholic acid but decreased those of alpha-muricholic acids in the feces of mice, suggesting that Boiogito decreased bile acid hydrophobicity in the intestinal lumen and attenuated farnesoid X receptor (FXR)-mediated responses in the intestine. Boiogito elevated the fecal levels of cholesterol and reduced the levels of hepatic lipids, which were supposed to be due to the attenuations of cholesterol solubilization in the intestinal lumen and FXR activation in the intestine.
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Academic Significance and Societal Importance of the Research Achievements |
漢方薬が腸管内胆汁酸の疎水性を低くすることや、腸管におけるFXR活性を低下させることが、腸管でのコレステロールの吸収を抑制したり、肝臓の脂質代謝を改善したりする可能性を、動物実験において示すことができた。これによって腸管内胆汁酸を介する漢方薬の有効性の科学的根拠を明示することができ、漢方薬理学の進展に寄与できたと考える。また本研究の結果によって、漢方薬の臨床的利用がすすみ、高額医薬品の使用が抑えられ、医療費負担軽減につながると期待できる。
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Report
(4 results)
Research Products
(16 results)