Clinical application of flavonoids as a support for pharmacotherapy

• Project/Area Number: 21700772
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Eating habits, studies on eating habits
• Research Institution: Osaka Ohtani University
• Principal Investigator: MIURA Takeshi 大阪大谷大学, 薬学部, 助教 (60434809)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 特殊栄養 / フラボノイド / 薬物治療 / 相互作用

Research Abstract

Bacterial expression and purification of CBR1, CBR3 and AKR1A1 fused with 6xHis cluster was successfully carried out. Kinetic analyses revealed that some extracts from fruit or vegetable strongly inhibit the enzymatic activities of CBR1 with IC50 of approximately 0.03% (v/v). Furthermore, the inhibitory effects were detected in cells. One of food additives, BHA, was found to enhance the transcriptional activity of CBR1 gene through the activation of transcription factor, Nrf2. Isatin, a substrate of CBR1, was found to exacerbate kidney ischemia/reperfusion injury in rats, suggesting that CBR1 is a novel potential target for pharmacotherapy.

Research Products

• [Journal Article] Regulation of human carbonyl reductase 1(CBR1, SDR21C1) gene by transcription factor Nrf2 (2013)
  • Author(s): Takeshi Miura, Ayako Taketomi, Toru Nishinaka, Tomoyuki Terada
  • Journal Title: Chemico-Biological Interactions Volume: 202(1-3) Pages: 126-135
  • Peer Reviewed
• [Journal Article] Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2 (2013)
  • Author(s): Takeshi Miura, Ayako Taketomi, Toru Nishinaka, Tomoyuki Terada
  • Journal Title: Chemico-Biological Interactions Volume: 202(1-3) Issue: 1-3 Pages: 126-135
  • DOI: 10.1016/j.cbi.2012.11.023
  • Peer Reviewed
• [Journal Article] Regulation of Aldo-keto reductase AKR1B10 gene expression: involvement of transcription factor Nrf2 (2011)
  • Author(s): Toru Nishinaka, Takeshi Miura, Manami Okumura, Fumika Nakao, Haruka Nakamura, Tomoyuki Terada
  • Journal Title: Chemico-Biological Interactions Volume: 191(1-3) Pages: 185-191
  • Peer Reviewed
• [Journal Article] Tsutomu NishiharaSite-directed mutagenesis of rat thioltransferase: effects of essential cyctein residues for the protection against oxidative stress (2010)
  • Author(s): Tomoyuki Terada, Kei-ichi Okamoto, Junichi Nishikawa, Takeshi Miura, Toru Nishinaka
  • Journal Title: Journal of Biochemistry and Molecular Toxicology Volume: 24(2) Pages: 60-65
  • Peer Reviewed
• [Journal Article] Tomoyuki TeradaImportance of the substrate-binding loop region of human monomeric carbonylreductases in catalysis and coenzyme binding (2009)
  • Author(s): Takeshi Miura, Toru Nishinaka
  • Journal Title: Life Sciences Volume: 85(7-8) Pages: 303-308
  • Peer Reviewed
• [Journal Article] Kazuya Yonezawa Relationship between aging and dosage of warfarin: the current status of warfarin anticoagulation therapy for Japanese outpatients in a department of cardiovascular medicine (2009)
  • Author(s): Takeshi Miura, Toru Nishinaka, Tomoyuki Terada
  • Journal Title: Journal of Cardiology Volume: 53 Pages: 355-360
  • Peer Reviewed
• [Presentation] 三浦健ら シスプラチン誘発性腎障害に対する alpha2受容体遮断薬の効果について (2013)
  • Author(s): 筒居秀伸
  • Organizer: 第133回日本薬学会年会
  • Place of Presentation: 横浜
• [Presentation] Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2 (2012)
  • Author(s): Ayako Taketomi, Takeshi Miura et al.
  • Organizer: 16th International workshop onEnzymology and Molecular Biology ofCarbonyl Metabolism
  • Place of Presentation: ドイツ
• [Presentation] 三浦健ら転写因子 Nrf2 による、ヒト単量体カルボニル還元酵素 1(CBR1)遺伝子の転写制御 (2012)
  • Author(s): 武富彩子
  • Organizer: 第132回日本薬学会年会
  • Place of Presentation: 札幌
• [Presentation] 三浦健らヒト単量体カルボニル還元酵素(CBR1)は、転写因子 Nrf2 によって制御される (2012)
  • Author(s): 武富彩子
  • Organizer: 第62回日本薬学会近畿支部総会
  • Place of Presentation: 西宮
• [Presentation] Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2 (2012)
  • Author(s): Ayako Taketomi, Takeshi Miura, et al.
  • Organizer: 16th International workshop on Enzymology and Molecular Biology of Carbonyl Metabolism
  • Place of Presentation: Kiel, Germany
• [Presentation] ヒト単量体カルボニル還元酵素(CBR1)は、転写因子Nrf2によって制御される (2012)
  • Author(s): 武富彩子 三浦健ら
  • Organizer: 第62回 日本薬学会近畿支部総会・大会
  • Place of Presentation: 西宮
• [Presentation] 筒居秀伸らラット腎虚血再灌流障害に対する内因性モノアミンオキシダーゼ阻害物質イサチンの効果 (2010)
  • Author(s): 三浦健
  • Organizer: 第130回日本薬学会年会
  • Place of Presentation: 岡山
• [Presentation] The effect of monoamine oxidase inhibtor on ischemia/reperfusion-induced acute kidney injury in rats (2010)
  • Author(s): Hidenobu Tsutsui, Takeshi Miura et al
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] Potential targeting region for the specific inhibition of human monomeric carbonyl reductases of the short-chain dehydrogenase/reductase superfamily (2009)
  • Author(s): Takeshi MIURA et al.
  • Organizer: 3rd Asian Pacific ISSX Regional Meeting
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2009-05-11
• [Presentation] Potential targeting region for the specific inhibition of human monomeric carbonyl reductases of the short-chain dehyhdrogenase/reductase superfamily Meeting (2009)
  • Author(s): Takeshi Miura et al
  • Organizer: 3rd Asian Pacific ISSX Regional
  • Place of Presentation: タイ