Yukiko Matsuo

Triterpene Glycosides from the Underground Parts of Caulophyllum thalictroides

A total of 22 triterpene glycosides, including 10 new compounds (1-10), were isolated from the underground parts of Caulophyllum thalictroides. The structures of the new glycosides were determined on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. All 22 compounds were evaluated for cytotoxicity against HL-60 human leukemia cells. The triterpene monodesmosides based on oleanolic acid (1 and 11-16) showed cytotoxic activity against HL-60 cells with IC(50) values that ranged from 3.4 to 15.9 microg/mL.

Steroidal glycosides from the bulbs of Bessera elegans and their cytotoxic activities

Examination of the bulbs of Bessera elegans (Liliaceae) led to isolation of nine new and five known steroidal glycosides. The structures of the nine compounds were determined based on the results of spectroscopic analysis, including two-dimensional NMR, and hydrolysis followed by chromatographic and spectroscopic analysis. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human diploid fibroblasts. One compound, the pseudo-furostanol glycoside, induced apoptosis in HL-60 and A549 cells in a time-dependent manner and cell-cycle arrest at the G0/G1 phase in A549 cells.

New Steroidal Glycosides from Rhizomes of Clintonia udensis

A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6–8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC50 values of 3.2±0.02, 2.2±0.12, and 2.2±0.06 μg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 μg/ml.

Steroidal glycosides from the bulbs of Fritillaria meleagris and their cytotoxic activities.

Steroidal glycosides (1-18), including 10 new compounds (1-10), were isolated from the bulbs of Fritillaria meleagris (Liliaceae). The structures of the new compounds were determined by two-dimensional (2D) NMR analysis, and by hydrolytic cleavage followed by spectroscopic and chromatographic analysis. The isolated compounds and their aglycones were evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells. Morphological observation and flow cytometry analysis showed that 5β-spirostanol glycoside (2) and a cholestane derivative (17a) induced apoptotic cell death in HL-60 cells through different mechanisms of action. Furthermore, the (22R)-spirosolanol glycoside (11) selectively induced apoptosis in A549 cells without affecting the caspase-3 activity level.

α-Santalol derivatives from Santalum album and their cytotoxic activities

A bioassay-guided fractionation of the heartwood of Santalum album led to the isolation of seven α-santalol derivatives including (9S,10E)-9-hydroxy-α-santalal, (10R,11S)-10,11-dihydroxy-α-santalol, (9E)-11,13-dihydroxy-α-santalol, and (10E)-12-hydroxy-α-santalic acid. Their structures were determined on the basis of results of spectroscopic analysis, including two-dimensional (2D) NMR spectroscopic data. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and TIG-3 normal human diploid fibroblasts. Of these (9S,10E)-9-hydroxy-α-santalal, exhibited tumor-selective cytotoxicity. The apoptosis induction properties of sesquiterpenes with cytotoxic potency in HL-60 cells are also described.

Novel Steroidal Glycosides from the Bulbs of Lilium pumilum.

Examination of the bulbs of Lilium pumilum (Liliaceae) led to the isolation of four novel steroidal glycosides (1–4) with a 2,3,4-trisubstituted β-d-glucopyranosyl unit. In 1 and 3, the α-l-arabinopyranosyl moiety is linked to C-3 of the inner trisubstituted β-d-glucopyranosyl group and is present as an usual 4C1 conformation. In contrast, in 2 and 4, the α-l-arabinopyranosyl moiety, which is attached to C-4 of the inner trisubstituted β-d-glucopyranosyl group, is present as a 1C4 conformation. The structures of the new steroidal glycosides were determined based on the results of spectroscopic analyses, including two-dimensional (2D) NMR data and hydrolysis.

Functional Analysis of Natural Polyphenols and Saponins as Alternative Medicines

Hiroshi Sakagami1, Tatsuya Kushida2, Toru Makino3, Tsutomu Hatano4, Yoshiaki Shirataki5, Tomohiko Matsuta1, Yukiko Matsuo6 and Yoshihiro Mimaki6 1Meikai University School of Dentistry, Saitama, 2Non-Profit Organization Bio-Knowledge Bank, Tokyo, 3HumaLabo Co., Ltd., Tokyo, 4Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 5Faculty of Pharmaceutical Sciences, Josai University, Saitama, 6Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Tokyo, Japan

Furostanol glycosides from the rhizomes of Helleborus orientalis

Eight new furostanol glycosides (1–8), together with two known ones (9 and 10), have been isolated from a glycoside-enriched fraction prepared from the rhizomes of Helleborus orientalis (Ranunculaceae). The structures of 1–8 were determined on the basis of extensive spectroscopic analysis, including 2D NMR, and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activity against HSC-2 cells.

Cardenolide glycosides from the seeds of Digitalis purpurea exhibit carcinoma-specific cytotoxicity toward renal adenocarcinoma and hepatocellular carcinoma cells

Four cardenolide glycosides, glucodigifucoside (2), 3′-O-acetylglucoevatromonoside (9), digitoxigenin 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-3-O-acetyl-β-D-digitoxopyranoside (11), and purpureaglycoside A (12), isolated from the seeds of Digitalis purpurea, exhibited potent cytotoxicity against human renal adenocarcinoma cell line ACHN. These compounds exhibited significantly lower IC50 values against ACHN than that against normal human renal proximal tubule-derived cell line HK-2. In particular, 2 exhibited the most potent and carcinoma-specific cytotoxicity, with a sixfold lower IC50 value against ACHN than that against HK-2. Measurement of cyclin-dependent kinase inhibitor levels revealed that upregulation of p21/Cip1 expression was involved in the carcinoma-specific cytotoxicity of 2. Further, compound 2 also exhibited the carcinoma-specific cytotoxicity toward hepatocellular carcinoma cell line. Graphical Abstract Glucodigifucoside (compound 2) from the seeds of Digitalis purpurea exhibit carcinoma-specific cytotoxicity towards renal adenocarcinoma cells in p53/p21-dependent manner.

Structural Characterization of Cholestane Rhamnosides from Ornithogalum saundersiae Bulbs and Their Cytotoxic Activity against Cultured Tumor Cells

Previous phytochemical studies of the bulbs of Ornithogalum saundersiae, an ornamental perennial plant native to South Africa, resulted in the isolation of 29 new cholestane glycosides, some of which were structurally unique and showed potent cytotoxic activity against cultured tumor cell lines. Therefore, we aimed to perform further phytochemical examinations of methanolic extracts obtained from Ornithogalum saundersiae bulbs, isolating 12 new cholestane rhamnosides (1–12) and seven known compounds (13–19). The structures of the new compounds (1–12) were identified via NMR-based structural characterization methods, and through a sequence of chemical transformations followed by spectroscopic and chromatographic analysis. The cytotoxic activity of the isolated compounds (1–19) and the derivatives (1a and 6a) against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells was evaluated. Compounds 10–12, 16, and 17 showed cytotoxicity against both HL-60 and A549 cells. Compound 11 showed potent cytotoxicity with an IC50 value of 0.16 µM against HL-60 cells and induced apoptotic cell death via a mitochondrion-independent pathway.