Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae).
Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae).
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DOI：
10.1016/j.jep.2010.03.008
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发表时间：
2010-05-27
影响因子：
5.4
通讯作者：
Mahady, Gail B.
中科院分区：
文献类型：
--
作者：
Michel, Joanna L.;Chen, Yegao;Zhang, Hongjie;Huang, Yue;Krunic, Aleksej;Orjala, Jimmy;Veliz, Mario;Soni, Kapil K.;Soejarto, Djaja Doel;Caceres, Armando;Perez, Alice;Mahady, Gail B.
关键词：
Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q’eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors. To investigate the estrogenic and serotonergic activities of P. hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7. The effects of the P. hispidum leaf extracts were investigated in estrogen reporter gene and endogenous gene assays in MCF-7 cells to determine if the extracts acted as an estrogen agonist or antagonist. In addition, the active compounds were isolated using ER- and 5-HT7 receptor bioassay-guided fractionation. The structures of the purified compounds were identified using high-resolution LC-MS and NMR spectroscopic methods. The ER- and 5-HT7-agonist effects of the purified chemical constituents were tested in a 2ERE-reporter gene assay in MCF-7 cells and in serotonin binding and functionalized assays. Three butenolides including one new compound (1) were isolated from the leaves of P. hispidum, and their structures were determined. Compound 1 bound to the serotonin receptor 5-HT7 with IC50 values of 16.1 and 8.3 μM, respectively, and using GTP shift assays, compound 1 was found to be a partial agonist of the 5-HT7 receptor. The P. hispidum leaf extracts, as well as compounds 2 and 3 enhanced the expression of estrogen responsive reporter and endogenous genes in MCF-7 cells, demonstrating estrogen agonist effects. Extracts of P. hispidum act as agonists of the ER and 5-HT7 receptors. Compound 1, a new natural product, identified as 9, 10-methylenedioxy-5,6-Z-fadyenolide, was isolated as the 5-HT7 agonist. Compounds 2 and 3 are reported for the first time in P. hispidum, and identified as the estrogen agonists. No inhibition of CYP450 was observed for any of these compounds in concentrations up to 1 μM. These activities are consistent with the Q’eqchi traditional use of the plant for the treatment of disorders associated with the female reproductive cycle.
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影响因子：
1.7
作者：
Ganzera, M;Khan, IA
通讯作者：
Khan, IA
影响因子：
1.4
作者：
Lago, João Henrique G.;Tanizaki, Tatiane M.;Kato, Massuo J.
通讯作者：
Kato, Massuo J.
影响因子：
5.1
作者：
Alécio, AC;Bolzani, VD;Furlan, M
通讯作者：
Furlan, M
DOI：
10.1097/gme.0b013e3181a4c76a
发表时间：
2009-07
期刊：
Menopause (New York, N.Y.)
影响因子：
--
作者：
Doyle BJ;Frasor J;Bellows LE;Locklear TD;Perez A;Gomez-Laurito J;Mahady GB
通讯作者：
Mahady GB
影响因子：
5.4
作者：
Michel, Joanna;Duarte, Reinel Eduardo;Mahady, Gail B.
通讯作者：
Mahady, Gail B.