Chemical study of effective constituents of Vietnamese ginseng-structure-activity relationship of anti-tumor-promoting activity-

越南人参有效成分的化学研究-抗肿瘤活性的构效关系-

• 批准号: 09672145
• 负责人: YAMASAKI Kazuo
• 金额: $ 2.3万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672145/
• 关键词: Vietnamese ginseng; Panax vietnamensis; ocotillol saponin; majonoside R2; anti-tumor promotion; Raji cells; TPA; fumonisin B1; majonoside-R2; サポニン

From the rhizomes and roots of Panax vietnamensis, 37 saponins including 14 new compounds were isolated and characterized. Among them, 21 saponins were already isolated from other species of the same genus, such as protopanaxadiol-type saponins : ginsenosides-Rb_1, -Rd., -Re, protopanaxatriol-type saponins : ginsenoside-Rg_1, and notoginsenoside. In addition, ocotillol-type saponins : majonoside R1 and remarkably high yield of majonoside R2 (MR2) were identified.To search for possible anti-tumor promoters, we measured the inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 'EPA.Methanol extract of Panax vietnamensis showed significant inhibitory activity. Since the activity was concentrated to the saponin fraction, the major saponins of this plant were tested. Among them, the major saponin, majonoside R2 (MR2) exhibited the strongest inhibitory effects on EBV-EA activation. This activity was unique to ocotillol skeleton.The effects of MR2 on the cell cycle of Raji cells treated with TPA were examined by flow cytometry. By the treatment with MR2, the ratio of S phase of Raji cells was increased, but the ratio of G_2 + M phases were decreased in dose-dependent manner. The inhibition mechanism of MR2 against cancer promotion of TPA was through influencing the cell cycle.On the basis of the above in vitro assay, in vivo assay was carried out. The inhibitory effect of MR2 on the two-stage carcinogenesis test of mouse skin tumor using DMBA as an initiator, and TPA and fumonsin B1 as the promoter. The papilloma production promoted by TPA and fumonisin B1 was significantly decreased and delayed by the pre-treatment of MR2. The activity of MR2 was higher than that of glycyrrhetic acid. In addition, the inhibitory effect on hepatic tumorigenesis initiated with DEN and promoted with pentobarbital was observed by oral administration of MR2.In conclusion, MR2, unique ocotillol saponin, promises to be cancer preventive lead compound.

从越南人参的根茎和根中分离鉴定了37个皂苷类化合物，其中包括14个新化合物。其中21个皂苷类化合物已从该属其它植物中分离得到，如原人参二醇型皂苷：人参皂苷-Rb_1，-Rd.，-Re，原人参三醇型皂苷：人参皂苷-Rg_1和三七皂苷。此外，还鉴定出了一种新的ocotillol型皂苷：majonoside R1和极高产率的majonoside R2（MR 2）。为了寻找可能的抗肿瘤促进剂，我们测定了越南人参甲醇提取物对EPA诱导的EB病毒早期抗原（EBV-EA）活化的抑制作用。由于活性集中于皂苷级分，因此测试了该植物的主要皂苷。其中主要皂苷majonoside R2（MR 2）对EBV-EA活化的抑制作用最强。流式细胞仪检测MR 2对TPA处理的Raji细胞周期的影响。MR 2处理后，Raji细胞S期比例增加，G2 + M期比例降低，呈剂量依赖性。MR 2对TPA促癌作用的抑制机制是通过影响细胞周期来实现的，在上述体外实验的基础上，进行了体内实验。MR 2对以DMBA为引发剂，TPA和伏蒙菌素B1为促进剂的小鼠皮肤肿瘤两阶段致癌试验的抑制作用。由TPA和伏马菌素B1促进的乳头状瘤的产生被MR 2的预处理显著降低和延迟。MR 2的活性高于大黄酸。此外，口服MR 2对DEN诱发的、戊巴比妥促进的肝肿瘤的发生也有抑制作用。结论：MR 2是一种独特的奥科替洛尔皂苷，有望成为一种抗癌先导化合物。

项目成果

Takao KONOSHIMA,Midori TAKASAKI,Harukuni TOKUDA,Hoyoku NISHINO,Nguyen Minh DUC,Ryoji KASAI,and Kazuo YAMASAKI: "Anti-tumor-promoting Activity of Majonoside-R2 from Vietnamese Ginseng, Panax vietnamensis HA et GRUSHV.(I)." Biological & Pharmaceutical Bulle

Takao KONOSHIMA、Midori TAKASAKI、Harukuni TOKUDA、Hoyoku NISHINO、Nguyen Minh DUC、Ryoji KASAI 和 Kazuo YAMASAKI：“来自越南人参、越南人参 HA 等 GRUSHV 的 Majonoside-R2 的抗肿瘤促进活性。(I)。”

Takao KONOSHIMA: "Anti-tumor-promoting Activity of Majonoside-R2 from Vietnamese Ginseng,Panax vietnamensis HA et GRUSHV.(I)" Biological & Pharmaceutical Bulletin. 21. 834-838 (1998)

Takao KONOSHIMA：“来自越南人参、越南人参 HA 等 GRUSHV 的 Majonoside-R2 的抗肿瘤促进活性。(I)”