RESUMEN
Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.
Asunto(s)
Phoeniceae/química , Extractos Vegetales/farmacología , Receptores Citoplasmáticos y Nucleares/agonistas , Células CACO-2 , Humanos , Técnicas In Vitro , Ligandos , Receptores Citoplasmáticos y Nucleares/genéticaRESUMEN
Boron affects human steroid hormone levels. Circulating testosterone and estradiol levels have been proposed to modify prostate cancer risk. However, the association between dietary boron intake and the risk of prostate cancer has not been evaluated by any epidemiological study. We explored the association between dietary boron intake and the risk of prostate cancer in the USA. Our analysis was based on data from the third National Health and Nutrition Examination Survey (NHANES III). Cross-sectional case-control study design was employed by comparing boron intake of 95 prostate cancer cases with that of 8,720 male controls. After controlling for age, race, education, smoking, body mass index, dietary caloric intake, and alcohol consumption, increased dietary boron intake was associated with a decreased risk of prostate cancer with a dose-response pattern. The adjusted odds ratio was 0.46 (95% confidence interval: 0.21-0.98) for the highest quartile of boron intake comparing to the lowest quartile (P for trend = 0.0525). The observed association should be interpreted with caution because of the small case sample size and the nature of the cross-sectional study design, but deserve further investigation.