Identification of chemopreventive component to cancer in shochu post-distillation slurry for its utilization as the raw material of functional food.

• Project/Area Number: 17510071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental technology/Environmental materials
• Research Institution: Kumamoto University
• Principal Investigator: MORIMURA Shigeru Kumamoto University, Graduate School of Science and Technology, Associate Professor, 大学院自然科学研究科, 助教授 (20230146)
• Co-Investigator(Kenkyū-buntansha): KIDA Kenji Kumamoto University, Graduate School of Science and Technology, Professor, 大学院自然科学研究科, 教授 (00195306) ; 重松 亨 熊本大学, 大学院・自然科学研究科, 助手 (10315286)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: shochu post-distillation slurry / vinegar / antitumor / apoptosis / antiradical / U937 / tyrosol / tryptophol / 抗ラジカル活性 / 免疫増強作用 / 精製 / 免疫増強

Research Abstract

We produced functional vinegar (vinegar) from shochu post-distillation slurry (SPDS) by using acetogen. We found that both of vinegar and SPDS showed antioxidant and apoptosis inducing activity. Their active components we re isolated and identified as tyrosol for antioxidant and tryptophol for apoptosis induction. Firstly, we demonstrated ed the antioxidant activity for human hepatoma cells HepG2 using H_2O_2induced oxidative stress model and mouse using CCl_4-induced acute liver injury model. Treatment of SPDS, vinegar, and tyrosol protected HepG2 from H_2O_2-induced oxidative stress by suppression of lipid peroxidation and GSH depletion. Moreover, we demonstrated that oral administration of them before treatment of CCl_4 significantly suppressed liver lipid peroxidation, GSH depletion, and reduction of GSH-dependent enzyme activities and inhibited liver inflammation in the acute mouse liver injury model. Secondly, we have investigated an apoptosis inducing component. An ethyl acetate-soluble fraction of vinegar was shown to suppress cell proliferation of U937 cells strongly. Fragmentation of DNA and morphological change showing apoptotic bodies were observed in U937 cells by the treatment of tryptophol. Tryptophol was found to be contained in the rice-, sweet potato-, barley-SPDS and in vinegars produced from them. Tryptophol was produced during ethanol fermentation but not in acetic acid fermentation and was found to be a second metabolic product of the tryptophan in ethanol fermentation. Immunoblot analysis showed the cleavage of caspase-8 and caspase-3 followed by cleavage of PARP in U937 cells treated with tryptophol, however, caspase-9 was not cleaved. We also revealed tryptophol induced the DISC formation including DR5 using immunoprecipitation and immunoblot analysis.

Research Products

• [Journal Article] Isolation of tryptophol as an apoptosis-inducing component of vinegar produced from boiled extract of black soybean in human monoblastic leukemia U937 cells (2007)
  • Author(s): Inagaki, S., Morimura, S., Gondo, K., Tang, Y.Q., Akutagawam H., Kida, K.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 71(2) Pages: 371-379
  • NAID: 10027511288
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] エタノール発酵過程で生成するアポトーシス誘導物質・トリプトフオール (2007)
  • Author(s): 稲垣秀一郎, 森村 茂, 権藤和修, 湯 岳琴, 芥川浩志, 木田建次
  • Journal Title: 日本醸造協会誌 102(3) Pages: 222-224
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Isolation of tryptophol as an apoptosis-inducing component of vinegar produced from boiled extract of black soybean in human monoblastic leukemia U937 cells. (2007)
  • Author(s): Inagaki, S., Morimura, S., Gondo, K., Tang, Y.Q., Akutagawam H., Kida, K.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 71 (2) Pages: 371-379
  • NAID: 10027511288
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tryptophol, apoptosis inducing component produced in ethanol fermentation process. (2007)
  • Author(s): Inagaki, S., Morimura, S., Gondo, K., Tang, Y.Q., Akutagawa, H., Kida, K.
  • Journal Title: Journal of the Brewing Society of Japan 102 (3) Pages: 222-224
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] エタノール発酵過程で生成するアポトーシス誘導物質・トリプトフォール (2007)
  • Author(s): 稲垣秀一郎, 森村 茂, 権藤和修, 湯岳琴, 芥川浩志, 木田建次
  • Journal Title: 日本醸造協会誌 102(3) Pages: 222-224
  • NAID: 10018891887
• [Journal Article] Apoptosis induction by vinegar produced from black soybean boiled extract in human monoblastic leukemia U937 cells : difference in cell toxic sensitivity compared to normal lymphocytes. (2006)
  • Author(s): Inagaki, S., Morimura, S., Shigematsu, T., Kida, K., Akutagawa, H.
  • Journal Title: Food Science and Technology Research 掲載決定
• [Journal Article] Apoptosis induction by vinegar produced from black soybean boiled extract in human monoblastic leukemia U937 cells : difference in cell toxic sensitivity compared to normal lymphocytes. (2005)
  • Author(s): Inagaki, S., Morimura, S., Shigematsu, T., Kida, K, Akutagawa, H.
  • Journal Title: Food Science and Technology Research 11(3) Pages: 311-317
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Apoptosis induction by vinegar produced from black soybean boiled extract in human monoblastic leukemia U937 cells : difference in cell toxic sensitivity compared to normal lymphocytes. (2005)
  • Author(s): Inagaki, S., Morimura, S., Shigematsu, T., Kida, K, Akutagawa, H.
  • Journal Title: Food Science and Technology Research 11 (3) Pages: 311-317
  • Description: 「研究成果報告書概要(欧文)」より