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Diarylheptanoid Phytoestrogens Isolated from the Medicinal Plant Curcuma comosa : Biologic Actions in Vitro and in Vivo Indicate Estrogen Receptor–Dependent Mechanisms

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Bibliographische Detailangaben
Titel: Diarylheptanoid Phytoestrogens Isolated from the Medicinal Plant Curcuma comosa : Biologic Actions in Vitro and in Vivo Indicate Estrogen Receptor–Dependent Mechanisms
Autoren: Winuthayanon, Wipawee, Piyachaturawat, Pawinee, Suksamrarn, Apichart, Ponglikitmongkol, Mathurose, Arao, Yukitomo, Hewitt, Sylvia C, Korach, Kenneth S
Quelle: Environ Health Perspect
Verlagsinformationen: Environmental Health Perspectives, 2009.
Publikationsjahr: 2009
Schlagwörter: 0301 basic medicine, Phytoestrogens - chemistry, Genetic - drug effects, Inbred C57BL, Polymerase Chain Reaction, Estrogen Receptor alpha - physiology, Estrogen - antagonists & inhibitors, Uterus - drug effects, Mice, Plant Extracts - pharmacology, Receptors, Fulvestrant, Mice, Knockout, 0303 health sciences, Tumor, Estrogen - physiology, Estradiol, Diarylheptanoids - isolation & purification, Organ Size, Plants, Plant Extracts - isolation & purification, 3. Good health, Mutant Strains, Estrogen Receptor beta - antagonists & inhibitors, Estradiol - analogs & derivatives, Female, Plant Extracts - chemistry, Transcription, Uterus - cytology, Estrogen Receptor beta - physiology, Genetic - genetics, Knockout, Ovariectomy, Estrogen - genetics, Phytoestrogens, Diarylheptanoids - pharmacology, Estrogen Receptor alpha - genetics, Cell Line, 03 medical and health sciences, Estrogen Receptor alpha - antagonists & inhibitors, Curcuma, Diarylheptanoids, Cell Line, Tumor, Diarylheptanoids - chemistry, Animals, Estrogen Receptor beta, Humans, Phytoestrogens - isolation & purification, Cell Proliferation, Medicinal - chemistry, Plants, Medicinal, Phytoestrogens - pharmacology, Plant Extracts, Research, Organ Size - drug effects, Curcuma - chemistry, Estrogen Receptor alpha, Estrogen Receptor beta - genetics, Estradiol - pharmacology, Mice, Mutant Strains, Mice, Inbred C57BL, Cell Proliferation - drug effects
Beschreibung: Diarylheptanoids isolated from Curcuma comosa Roxb. have been recently identified as phyto estrogens. However, the mechanism underlying their actions has not yet been identified.We characterized the estrogenic activity of three active naturally occurring diarylheptanoids both in vitro and in vivo.We characterized mechanisms of estrogenic action of the diarylheptanoids (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (D1), 1,7-diphenyl-(6E)-6-hepten-3-one (D2), and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3) by using a real-time polymerase chain reaction assay, a mammalian transfection model, and a uterotrophic assay in mice.All diarylheptanoids up-regulated estrogen-responsive genes in estrogen-responsive breast cancer cells (MCF-7). In HepG2 cells transfected with estrogen receptor (ER) beta or different ERalpha functional receptor mutants and the Vit-ERE-TATA-Luc reporter gene, all diarylheptanoids induced transcription through a ligand-dependent human ERalpha-ERE-driven pathway, which was abolished with ICI 182,780 (ER antagonist), whereas only D2 was active with ERbeta. An ERalpha mutant lacking the functional AF2 (activation function 2) region was not responsive to 17beta-estradiol (E(2)) or to any of the diarylheptanoids, whereas ERalpha lacking the AF1 domain exhibited wild-type-like activity. D3 markedly increased uterine weight and proliferation of the uterine epithelium in ovariectomized mice, whereas D1 and D2 were inactive. D3, like E(2), up-regulated lactoferrin (Ltf) gene expression. The responses to D3 in the uterus were inhibited by ICI 182,780. In addition, D3 stimulated both classical (Aqp5) and nonclassical (Cdkn1a) ER-mediated gene regulation.The results suggest that the D3 diarylheptanoid is an agonist for ER both in vitro and in vivo, and its biological action is ERalpha selective, specifically requiring AF2 function, and involves direct binding via ER as well as ERE-independent gene regulation.
Publikationsart: Article
Other literature type
Sprache: English
ISSN: 1552-9924
0091-6765
DOI: 10.1289/ehp.0900613
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/19654927
https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.0900613
https://www.cabdirect.org/cabdirect/abstract/20093201176
https://europepmc.org/articles/PMC2717144/
https://pubmed.ncbi.nlm.nih.gov/19654927/
http://ehp.niehs.nih.gov/0900613
https://www.questia.com/library/journal/1G1-206048851/diarylheptanoid-phytoestrogens-isolated-from-the-medicinal
Rights: pd
PDM
Dokumentencode: edsair.doi.dedup.....02f4ab931bd0176d4205e7bf4c743fd2
Datenbank: OpenAIRE
Beschreibung
Abstract:Diarylheptanoids isolated from Curcuma comosa Roxb. have been recently identified as phyto estrogens. However, the mechanism underlying their actions has not yet been identified.We characterized the estrogenic activity of three active naturally occurring diarylheptanoids both in vitro and in vivo.We characterized mechanisms of estrogenic action of the diarylheptanoids (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (D1), 1,7-diphenyl-(6E)-6-hepten-3-one (D2), and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3) by using a real-time polymerase chain reaction assay, a mammalian transfection model, and a uterotrophic assay in mice.All diarylheptanoids up-regulated estrogen-responsive genes in estrogen-responsive breast cancer cells (MCF-7). In HepG2 cells transfected with estrogen receptor (ER) beta or different ERalpha functional receptor mutants and the Vit-ERE-TATA-Luc reporter gene, all diarylheptanoids induced transcription through a ligand-dependent human ERalpha-ERE-driven pathway, which was abolished with ICI 182,780 (ER antagonist), whereas only D2 was active with ERbeta. An ERalpha mutant lacking the functional AF2 (activation function 2) region was not responsive to 17beta-estradiol (E(2)) or to any of the diarylheptanoids, whereas ERalpha lacking the AF1 domain exhibited wild-type-like activity. D3 markedly increased uterine weight and proliferation of the uterine epithelium in ovariectomized mice, whereas D1 and D2 were inactive. D3, like E(2), up-regulated lactoferrin (Ltf) gene expression. The responses to D3 in the uterus were inhibited by ICI 182,780. In addition, D3 stimulated both classical (Aqp5) and nonclassical (Cdkn1a) ER-mediated gene regulation.The results suggest that the D3 diarylheptanoid is an agonist for ER both in vitro and in vivo, and its biological action is ERalpha selective, specifically requiring AF2 function, and involves direct binding via ER as well as ERE-independent gene regulation.
ISSN:15529924
00916765
DOI:10.1289/ehp.0900613