Development of New Chemopreventive Agents from Monascus pilosus-Fermented Rice (Red-Mold Rice)

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14572101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 医薬分子機能学
• Research Institution: Nihon University
• Principal Investigator: AKIHISA Toshihiro Nihon University, College of Science and Technology, Professor, 理工学部, 教授 (30060213)
• Co-Investigator(Kenkyū-buntansha): TOKUDA Harukuni Kyoto Prefectural University of Medicine, Department of Biochemistry, Assistant Professor, 生化学教室, 助手 (60111960) ; YASUKAWA Ken Nihon University, College of Pharmacy, Professor, 薬学部, 教授 (00130625)
• Project Period (FY): 2002 – 2004
• Keywords: Monascus pilosus / red-mold rice / azaphilones / furanoisophthalides / amino acids / antitumor-promoter / antitumor-initiator / two-stage carcinogenesis

Research Abstract

Six azaphilones, monascin (1), ankaflavin (2), rubropunctatin (3), monascorburin (4), rubropunctamine (5), and monascorburamine (6), two furanoisophthalides, xanthomonasin A (7) and xanthomonasin B (8), and two amino acids, (+)-monascumic acid (9) and (-)-monascumic acid (10), isolated from the extracts of Monascus pilosus-fermented rice (red-mold rice) were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced inflammation in mice, on the induction of Epstein-Barr virus early antigen(EBV-EA) by TPA in Raji cells, and on the activation of (±)-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide(NO) donor. Among the compounds tested, seven compounds (1-6,and 10) on TPA-induced inflammation, and six compounds (1,3-5,9,and 10) on EBV-EA activation, exhibited potent inhibitory effects. All of the compounds tested showed moderate inhibitory effects on NOR 1 activation. Compound 1 was further evaluated for its anti-tumor-initiating activity via oral administration on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO^-;PN) or by ultraviolet light B(UVB) as an initiator and 12-O-tetradecanoylphorbol-13-acetate(TPA) as a promoter. Compound 1 exhibited marked inhibitory activity on both PN and UVB induced mouse skin carcinogenesis tests. These findings suggest that compound 1 may be valuable as potential cancer chemopreventive agents in chemical and environmental carcinogenesis.

Research Products

• [Journal Article] Azaphilones, Furanoisophthalides, and Amino Acids from the Extracts of Monasucus pilosus-Fermented Rice (Red-Mold Rice) and Their Chemopreventive Effects (2005)
  • Author(s): 秋久俊博, 徳田春邦, 安川 憲ら
  • Journal Title: Journal of Agricultural and Food Chemistry 53 Pages: 562-565
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Azaphilones, Furanoisophthalides, and Amino Acids from the Extracts of Monascus pilosus-Fermented Rice (Red-Mold Rice) and Their Chemopreventive Effects (2005)
  • Author(s): Toshihiro Akihisa, Harukuni Tokuda, Ken Yasukawa, Motohiko Ukiya, Ayaka Kiyota, Naoyuki Sakamoto, Takashi Suzuki, Nobukazu Tanabe, Hoyoku Nishino
  • Journal Title: Journal of Agricultural and Food Chemistry 53(3) Pages: 562-565
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] (+)- and (-)-syn-2-Isobutyl-4-methylazetidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fermented Rice (Red-Mold Rice) (2004)
  • Author(s): 秋久俊博, 徳田春邦, 安川 憲ら
  • Journal Title: Journal of Natural Products 67 Pages: 479-480
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] (+)- and (-)-syn-2-Isobutyl-4-methylazethidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fexmented Rice (Red-Mold Rice) (2004)
  • Author(s): Toshihiro Akihisa, Shoichi Mafune, Motohiko Ukiya, Yumiko Kimura, Ken Yasukawa, Takashi Suzuki, Harukuni Tokuda, Nobukazu Tanabe, Tadahiko Fukuoka
  • Journal Title: Journal of Natural Products 67(3) Pages: 479-480
  • Description: 「研究成果報告書概要(欧文)」より