Diarylheptanoid phytoestrogens isolated from the medicinal plant Curcuma comosa: biologic actions in vitro and in vivo indicate estrogen receptor-dependent mechanisms

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

Modeling Europe with CAMx for the Air Quality Model Evaluation International Initiative (AQMEII)

The CAMx photochemical grid model was used to model ozone (O 3) and particulate matter (PM) over a European modeling domain for calendar year 2006 as part of the Air Quality Model Evaluation International Initiative (AQMEII). The CAMx base case utilized input data provided by AQMEII for emissions, meteorology and boundary conditions. Sensitivity of model outputs to input data was investigated by using alternate input data and changing other important modeling assumptions including the schemes to represent photochemistry, dry deposition and vertical mixing. Impacts on model performance were evaluated by comparisons with ambient monitoring data. Base case model performance for January and July 2006 exhibited under-estimation trends for all pollutants both in winter and summer, except for SO 2. SO 2 generally had little bias although some over-estimation occurred at coastal locations and this was attributed to incorrect vertical distribution of emissions from marine vessels. Performance for NOx and NO 2 was better in winter than summer. The tendency to under-predict daytime NOx and O 3 in summer may result from insufficient NOx emissions or overstated daytime dilution (e.g., too deep planetary boundary layer) or monitors that are located near sources (e.g., roadside monitors). Winter O 3 was biased low and this was attributed to a low bias in the O 3 boundary conditions. PM 10 was widely under-predicted in both winter and summer. The poor PM 10 was influenced by under-estimation of coarse PM emissions. Sensitivities of O 3 concentrations to precursor emissions are quantified using the decoupled direct method in CAMx. The results suggest that O 3 production over the central and southern Europe during summer is mostly NOx-limited but for a more northerly city, London, O 3 production can be limited either by NOx or VOC depending upon daily meteorological conditions. © 2011 Elsevier Ltd

Modeling Europe with CAMx for the Air Quality Model Evaluation International Initiative (AQMEII)

International audienceThe CAMx photochemical grid model was used to model ozone (O3) and particulate matter (PM) over a European modeling domain for calendar year 2006 as part of the Air Quality Model Evaluation International Initiative (AQMEII). The CAMx base case utilized input data provided by AQMEII for emissions, meteorology and boundary conditions. Sensitivity of model outputs to input data was investigated by using alternate input data and changing other important modeling assumptions including the schemes to represent photochemistry, dry deposition and vertical mixing. Impacts on model performance were evaluated by comparisons with ambient monitoring data. Base case model performance for January and July 2006 exhibited under-estimation trends for all pollutants both in winter and summer, except for SO2. SO2 generally had little bias although some over-estimation occurred at coastal locations and this was attributed to incorrect vertical distribution of emissions from marine vessels. Performance for NOx and NO2 was better in winter than summer. The tendency to under-predict daytime NOx and O3 in summer may result from insufficient NOx emissions or overstated daytime dilution (e.g., too deep planetary boundary layer) or monitors that are located near sources (e.g., roadside monitors). Winter O3 was biased low and this was attributed to a low bias in the O3 boundary conditions. PM10 was widely under-predicted in both winter and summer. The poor PM10 was influenced by underestimation of coarse PM emissions. Sensitivities of O3 concentrations to precursor emissions are quantified using the decoupled direct method in CAMx. The results suggest that O3 production over the central and southern Europe during summer is mostly NOx-limited but for a more northerly city, London, O3 production can be limited either by NOx or VOC depending upon daily meteorological conditions

Improvements of insulin resistance in ovariectomized rats by a novel phytoestrogen from <it>Curcuma comosa </it>Roxb

<p>Abstract</p> <p>Background</p> <p><it>Curcuma comosa </it>Roxb. (<it>C. comosa</it>) is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3<it>R</it>)-1,7-diphenyl-(4<it>E</it>,6<it>E</it>)-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of <it>C. comosa </it>in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks) of <it>C. comosa </it>hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats.</p> <p>Methods</p> <p>Female Sprague-Dawley rats were ovariectomized (OVX) and treated with <it>C. comosa </it>hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW)) and compound 049 (50 mg/kg BW) intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined.</p> <p>Results</p> <p>Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with <it>C. comosa </it>hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of <it>C. comosa </it>hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels.</p> <p>Conclusions</p> <p>Treatment with <it>C. comosa </it>and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.</p

Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: The GOASIA study

10.1186/s12876-020-01240-zBMC Gastroenterology2018