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

从越南参根茎和根中分离得到37个皂苷类化合物，其中14个为新化合物。其中21种皂苷已从同一属的其他种中分离得到，如原人参二醇型皂苷：人参皂苷- rb_1， -Rd。-Re，原人参皂苷型皂苷：人参皂苷- rg_1，三七皂苷。此外，还鉴定出了大黄油醇型皂苷：大黄油苷R1和产量显著的大黄油苷R2 （MR2）。为了寻找可能的抗肿瘤启动子，我们检测了EPA对eb病毒早期抗原（EBV-EA）活化的抑制作用。越参甲醇提取物具有显著的抑菌活性。由于活性被浓缩到皂苷部分，因此对该植物的主要皂苷进行了测试。其中，主要皂苷majonoside R2 （MR2）对EBV-EA活化的抑制作用最强。这种活性是ocotillol骨骼所特有的。流式细胞术检测MR2对TPA处理Raji细胞周期的影响。经MR2处理后，Raji细胞S相比例增加，G_2 + M相比例降低，呈剂量依赖性。MR2对TPA促癌作用的抑制机制是通过影响细胞周期。在上述体外实验的基础上，进行体内实验。MR2对以DMBA为引发剂，TPA和fumonsin B1为启动子的小鼠皮肤肿瘤两期癌变试验的抑制作用。经MR2预处理后，TPA和伏马菌素B1促进的乳头状瘤生成明显减少和延迟。MR2的活性高于甘草酸。此外，通过口服MR2观察到由DEN引发并由戊巴比妥促进的肝肿瘤发生的抑制作用。综上所述，MR2是独特的茴香醇皂苷，有望成为预防癌症的先导化合物。

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.