, Volume 26, Issue 8, pp 620-630

Proliferative effects of flavan-3-ols and propelargonidins from rhizomes ofDrynaria fortunei on MCF-7 and osteoblastic cells

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The proliferative effects of thirty Oriental medicinal herbs on MCF-7 (estrogen-sensitive breast cancer cell line) and ROS 17/2.8 osteoblast-like cells were determined using the MTT assay. Methanol extracts from several herbs was found to show proliferative activity on the above two cell lines in the range of 5 to 100 μg/mL. Among these active herbs, the methanol extract from the rhizomes ofDrynaria fortunei showed the most potent proliferative activity, and the cell proliferations were significantly increase by 136 and 158% in the MCF-7 and ROS 17/2.8 cells, respectively, when treated with 100 μg/mL Through a bioassay-guided separation, eight flavonoids, including four new flavan-3-ols and two propelargonidins, together with the known (-)-epiafzelechin and naringin, were isolated. Their chemical structures were characterized as (-)-epiafzelechin (1), (-)-epiafzelechin-3-O-β-D-allopyranoside (2), (-)-epiafzelechin-3-O-(6“-O-acetyl)-β-D-allopyranoside (3), 4β-carboxymethyl-(-)-epiafzelechin methyl ester (4), 4β-car-boxymethyl-(-)-epiafzelechin sodium salt (5), naringin (6), (-)-epiafzelechin-(4β→8)-4β-car-boxymethylepiafzelechin methyl ester (7) and (-)-epiafzelechin-(4β→8, 2β→O→7)-epiafzelechin-(4β→8)-epiafzelechin (8) by extensive 1D and 2D NMR spectroscopy. Most of these flavonoids, in the range of 10-15~10-6 M, accelerated the proliferation of MCF-7 cell, with compounds7 and8, in the range of 10-15~10-12 M, showing especially potent proliferation effects. Meanwhile, seven flavonoids, with the exception of compound4, stimulated the proliferation of ROS 17/2.8 cells in the range of 10-15~10-6 M, with compounds5-8 especially accelerating the proliferation, in dose-dependent manners (10-15~10-9 M), and their proliferative effect was much stronger than that of E2 and genistein. These results suggest that propelargonidin dimers and trimers isolated from the rhizomes ofDrynaria fortunei may be useful as potential phytoestrogens, which play important physiological roles in the prevention of postmenopausal osteoporosis.