Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects
Abstract Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid gly...
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2017
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oai:doaj.org-article:cdbf79c242b5456e9d71bb62e04b94112021-12-02T12:32:07ZFlavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects10.1038/s41598-017-08203-72045-2322https://doaj.org/article/cdbf79c242b5456e9d71bb62e04b94112017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08203-7https://doaj.org/toc/2045-2322Abstract Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1–4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.Fu LiBao-Wen DuDan-Feng LuWen-Xuan WuKanjana WongkrajangLun WangWen-Chen PuChang-Lu LiuHan-Wei LiuMing-Kui WangFei WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Fu Li Bao-Wen Du Dan-Feng Lu Wen-Xuan Wu Kanjana Wongkrajang Lun Wang Wen-Chen Pu Chang-Lu Liu Han-Wei Liu Ming-Kui Wang Fei Wang Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
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Abstract Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1–4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases. |
format |
article |
author |
Fu Li Bao-Wen Du Dan-Feng Lu Wen-Xuan Wu Kanjana Wongkrajang Lun Wang Wen-Chen Pu Chang-Lu Liu Han-Wei Liu Ming-Kui Wang Fei Wang |
author_facet |
Fu Li Bao-Wen Du Dan-Feng Lu Wen-Xuan Wu Kanjana Wongkrajang Lun Wang Wen-Chen Pu Chang-Lu Liu Han-Wei Liu Ming-Kui Wang Fei Wang |
author_sort |
Fu Li |
title |
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
title_short |
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
title_full |
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
title_fullStr |
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
title_full_unstemmed |
Flavonoid glycosides isolated from Epimedium brevicornum and their estrogen biosynthesis-promoting effects |
title_sort |
flavonoid glycosides isolated from epimedium brevicornum and their estrogen biosynthesis-promoting effects |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/cdbf79c242b5456e9d71bb62e04b9411 |
work_keys_str_mv |
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