Marine natural products. XIV. Structures of echinosides A and B, antifungal lanostane-oligosides from the sea cucumber Actinopyga echinites (Jaeger).
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Biomedical subjects
Publications and source records attributed to I Kitagawa.
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The effects of two plant glycosides, ginsenosides Rh1 and Rh2, on the growth and differentiation of mouse melanoma (B16) cells in culture were studied. These plant glycosides have a dammarane skeleton resembling a steroid skeleton as an aglycone. Ginsenoside Rh2 inhibits the growth of B16 melanoma cells, causes morphological alterations, and stimulates melanogenesis at high cellular density. When ginsenoside Rh2 was removed after 2 or 6 days of treatment, the growth rate recovered slightly but not completely, during the period of observation (4 days after removal). On the other hand, ginsenoside Rh1 does not inhibit the growth of melanoma cells even at concentrations over 100 microM but stimulates the expression of the melanotic phenotype. Ginsenosides Rh1 and Rh2, possessing a glucose molecule at C-6 and C-3, respectively, have very similar chemical structures, but their effects on B16 melanoma cells differ remarkably. While it appears that the degree of differentiation is inversely related to cell growth, the present observations suggest that the differentiation and growth capacity of this B16 melanoma subline are independent phenotypic expressions.
The stability of ginsenosides (Rb1, Rb2, and Rg1) in aqueous solutions of varying pH was studied kinetically at 37 degrees C and an ionic strength of 0.15, using reverse-phase high-performance liquid chromatography. Degradation readily occurred by a proton-catalyzed reaction, the half-lives being only approximately 30 min at pH 1. However, under neutral intestinal pH conditions, the degradation was almost negligible throughout the experimental period (approximately 40 h).
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The combined effects of paeoniflorin (PF), a main component of paeony roots, and glycyrrhizin (GLR), a main component of licorice roots, were investigated on isolated sciatic nerve-sartorius muscle preparations in frogs, or on isolated or in situ phrenic nerve-diaphragm muscle preparations in mice, intending to explain the effects of "Shakuyaku-Kanzô-Tô, composed of both these Chinese drugs, on clinical neuropathy. PF and GLR used together blocked indirectly stimulated twitchings at concentrations which when used alone induced no blocking effects. PF and GLR at a combining ratio of 1:2 (weight concentrations) corresponding to the amounts contained in "Shakuyaku-Kanzô-Tô, was more potent than when they were used at the ratio of 1:1 or 2:1. The synergistic effects induced by GLR were also confirmed for the other components, paeoniflorigenone or oxypaeoniflorin, which are contained in paeony roots, and for succinylcholine. The blocking effect of d-tubocurarine were not increased by GLR. Concludedly, PF and GLR were found to cause the pharmacological blend effect. The two combined compounds were mainly therapeutic components in "Shakuyaku-Kanzô-Tô".
AFP producing cancer of the stomach was divided into 2 groups; Group A demonstrated a marked elevation of serum AFP levels before gastrectomy and was positive for AFP by PAP staining; group B showed delayed elevation of AFP levels at recurrence or in the terminal stage. Experimentally, we could establish three cell lines from group A and two lines from group B from transplanted tumor in nude mice. Tumor growth, changes of serum AFP levels and PAP staining investigated in each group. Group A and B were not only thought to exhibit different biological behavior, but also different mechanisms in AFP production. Group A cells may have the ability to secrete high levels of AFP; this may be a property of these tumor cells. On the other hand, group B tumor cells initially have little ability to secrete AFP. However, they may transform into AFP producing cells as a phenomenon of cell differentiation.
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