Abstract
BackgroundResveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural antioxidant polyphenol able to exert a wide range of biological effect on several tissues. Despite its important beneficial properties, it has a low water solubility, which limits its therapeutic applications in humans. Resveratrol also acts as a phytoestrogen that modulates estrogen receptor (ER)-mediated transcription. In addition, it has been shown that ovarian tissues benefit greatly from vitamin D3, which exerts its beneficial effects through VDR receptors.The aim was to evaluate the cooperative effects of resveratrol combined with vitamin D3 on ovarian cells and tissues and some other organs as well. Moreover, the modulation of specific intracellular pathways involving ER and VDR receptors has been studied.MethodsThe experiments were performed both in vitro and in vivo, to analyze cell viability, radical oxygen species production, signal transductions through Western Blot, and resveratrol quantification by HPLC.ResultsCell viability, radical oxygen species production, and intracellular pathways have been studied on CHO-K1 cells. Also, the relative mechanism activated following oral intake in female Wistar rats as animal model was investigated, evaluating bioavailability, biodistribution and signal transduction in heart, kidney, liver and ovarian tissues. Both in in vitro and in vivo experiments, resveratrol exerts more evident effects when administered in combination with vitD in ovarian cells, showing a common biphasic cooperative effect: The role of vitamin D3 in maintaining and supporting the biological activity of resveratrol has been clearly observed. Moreover, resveratrol plus vitamin D3 blood concentrations showed a biphasic absorption rate.ConclusionsSuch results could be used as a fundamental data for the development of new therapies for gynecological conditions, such as hot-flashes.
Highlights
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural antioxidant polyphenol able to exert a wide range of biological effect on several tissues
The common incidence of hot flashes is around 75% and presently hormone replacement therapy is the gold standard in the management of moderate to severe vasomotor symptoms associated with menopause
Dose-response and time-course study A dose response and a time-course study were planned to identify the dose of Resveratrol (RES) able to induce the maximal effect on cell viability during time
Summary
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural antioxidant polyphenol able to exert a wide range of biological effect on several tissues. A number of epidemiologic studies have shown that RES has beneficial effects in preventing various pathologic conditions ranging from cardiovascular diseases to cancer [15]. RES displays a great affinity for ER behaving as either agonist or antagonist in a cell- and tissuespecific manner [23] This is important to explain the effectiveness of RES in reducing the number of vasomotor episodes and the intensity of hot flashes (HF), with the transition from moderate/severe to mild symptoms in 78.6% of patients [24]. RES has been associated with anti-inflammatory effects, in tissues that contain a large number of estrogen receptors, through this connection has been studied, but there are few studies on the mechanisms activated [25, 26]
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