| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
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.
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