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

红曲霉发酵米（红霉米）新型化学预防剂的研制

• 批准号: 14572101
• 负责人: AKIHISA Toshihiro
• 金额: $ 2.11万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572101/
• 关键词: Monascus pilosus; red-mold rice; azaphilones; furanoisophthalides; amino acids; antitumor-promoter; antitumor-initiator; two-stage carcinogenesis; アザフィロイド類色素; フラノソフタライド類色素; がん予防物質; EBV-EA発現抑制物質; TPA誘発マウス耳殻炎症抑制物質

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.

对从红曲霉发酵大米(红霉米)提取物中分离得到的6种氮杂环酮类化合物红曲菌素(1)、红曲霉毒素(2)、红曲霉毒素(3)、红曲霉毒素(4)、红曲霉酚丁胺(5)和单抗坏血酸(6)，两种呋喃异苯二甲酸酯(黄单胞菌素A(7)和黄单胞菌素B(8))以及两种氨基酸(+)-单胞酸(9)和(-)-单胞酸(10)对小鼠12-O-tetradecanoylphorbol-13-acetate(TPA)-induced炎症的抑制作用进行了研究。关于TPA在Raji细胞中诱导EB病毒早期抗原(EBV-EA)，以及对一氧化氮(NO)供体(±)-(E)-methyl-2[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide(NOR 1)激活的影响。在所测试的化合物中，有7个化合物(1-6和10)对TPA诱导的炎症反应有抑制作用，6个化合物(1，3-5，9和10)对EBV-EA活性有较强的抑制作用。所有受试化合物对NOR-1活性均有中等程度的抑制作用。以过氧亚硝酸根(ONOO)和紫外线B(UVB)为引发剂，12-O-十四酰佛波醇-13-乙酸酯(TPA)为促进剂，对过氧亚硝酸根(ONOO)和紫外线B(UVB)诱导的小鼠皮肤肿瘤的两步致癌作用进行了研究，进一步评价了化合物1的抗癌活性。化合物1对Pn和UVB诱导的小鼠皮肤癌变均有明显的抑制作用。这些发现表明，化合物1可能在化学致癌和环境致癌方面作为潜在的癌症化学预防药物。

项目成果

Azaphilones, furanoisophthalides, and amino acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects

• DOI: 10.1021/jf040199p
• 发表时间: 2005-02-09
• 期刊: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
• 影响因子: 6.1
• 作者: Akihisa, T;Tokuda, H;Nishino, H
• 通讯作者: Nishino, H

(+)- and (-)-syn-2-Isobutyl-4-methylazethidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fexmented Rice (Red-Mold Rice)

红曲发酵米（红霉米）提取物中的 ( )- 和 (-)-syn-2-异丁基-4-甲基氮杂环丁烷-2,4-二羧酸

• 发表时间: 2004
• 期刊: Journal of Natural Products 67(3)
• 作者: Toshihiro Akihisa;Shoichi Mafune;Motohiko Ukiya;Yumiko Kimura;Ken Yasukawa;Takashi Suzuki;Harukuni Tokuda;Nobukazu Tanabe;Tadahiko Fukuoka
• 通讯作者: Tadahiko Fukuoka

秋久俊博, 徳田春邦, 安川 憲ら: "(+)-and (-)-syn-2-Isobutyl-4-methylazetidine-2,4-dicarboxylic Acids from the Extract of Monascus pilosus-Fermented Rice (Red-Mold Rice)"Journal of Natural Products. 67巻3号(印刷中). (2004)

Toshihiro Akihisa、Harukuni Tokuda、Ken Yasukawa 等人：“红曲发酵米提取物中的 (+)-和 (-)-syn-2-异丁基-4-甲基氮杂环丁烷-2,4-二羧酸（红曲-）霉米）“天然产物杂志。第 67 卷，第 3 期（印刷中）。（2004 年）

Azaphilones, Furanoisophthalides, and Amino Acids from the Extracts of Monasucus pilosus-Fermented Rice (Red-Mold Rice) and Their Chemopreventive Effects

红曲菌发酵米（红霉米）提取物中氮杂菲酮类、呋喃间苯酞类和氨基酸及其化学预防作用

• 发表时间: 2005
• 期刊: Journal of Agricultural and Food Chemistry 53
• 作者: 秋久俊博;徳田春邦;安川 憲ら
• 通讯作者: 安川 憲ら

(+)- and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (Red-Mold Rice)

• DOI: 10.1021/np030394i
• 发表时间: 2004-03-01
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Akihisa, T;Mafune, S;Fukuoka, T
• 通讯作者: Fukuoka, T