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Trans-resveratrol (RESV), pterostilbene, trans-piceid and trans-viniferins are bioactive stilbenes present in grapes and other plants. Several groups applied biotechnology to introduce their synthesis in plant crops. Biochemical interaction with enzymes, regulation of non-coding RNAs, and activation of signaling pathways and transcription factors are among the main effects described in literature. However, solubility in ethanol, short half-life, metabolism by gut bacteria, make the concentration responsible for the effects observed in cultured cells difficult to achieve. Derivatives obtained by synthesis, trans-resveratrol analogs and methoxylated stilbenes show to be more stable and allow the synthesis of bioactive compounds with higher bioavailability. However, changes in chemical structure may require testing for toxicity. Thus, the delivery of RESV and its natural analogs incorporated into liposomes or nanoparticles, is the best choice to ensure stability during administration and appropriate absorption. The application of RESV and its derivatives with anti-inflammatory and anticancer activity is presented with description of novel clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action., Methods: Human endothelial cells were incubated with increasing concentrations (1-50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1-25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial-monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1., Results: Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress., Conclusions: This study showed multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including atherosclerosis.

The plant polyphenol trans-resveratrol (3, 5, 4'-trihydroxystilbene) mainly found in grape, peanut and other few plants, displays a wide range of biological effects. Numerous in vitro studies have described various biological effects of resveratrol. In order to provide more information regarding absorption, metabolism, and bioavailability of resveratrol, various research approaches have been performed, including in vitro, ex vivo, and in vivo models. In recent years, the induction of resveratrol synthesis in plants which normally do not accumulate such polyphenol, has been successfully achieved by molecular engineering. In this context, the ectopic production of resveratrol has been reported to have positive effects both on plant resistance to biotic stress and the enhancement of the nutritional value of several widely consumed fruits and vegetables. The metabolic engineering of plants offers the opportunity to change the content of specific phytonutrients in plant - derived foods. This review focuses on the latest findings regarding on resveratrol bioproduction and its effects on the prevention of the major pathological conditions in man.

Carcinoma progression is associated with the loss of epithelial features, and the acquisition of a mesenchymal phenotype by tumour cells. Herein we show that exposure of MCF-7 cells to epidermal growth factor (EGF) resulted in morphological alterations characteristic of epithelial-to-mesenchymal transition (EMT). EGF treatment resulted in increased motility along with an up-regulation of transcription factors Slug, Zeb1, Zeb2, and mesenchymal markers Vimentin and N-cadherin. Treatment of MCF-7 cells with a combined stimulation of EGF and resveratrol, a naturally occurring stilbene with antitumor properties, failed to alter cell morphology, motility and overexpression of EMT markers induced by EGF. Using specific chemical inhibitors, we demonstrated that EGF-induced EMT is mediated by extracellular signal-regulated kinase 1/2 (ERK 1/2) signalling pathway and that resveratrol is able to repress EGF-induced ERK activation. In summary, these data provide new evidence of the inhibitory effect of resveratrol on EGF-induced EMT cell transformation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Resveratrol, a plant phenolic compound, is found in grapes and red wine, but is not widely distributed in other common food sources. The pathway for resveratrol biosynthesis is well characterized. Metabolic engineering of this compound has been achieved in tomato plants (Lycopersicon esculentum Mill.) in order to improve their nutritional value. Tomato plants synthesizing resveratrol were obtained via the heterologous expression of a grape (Vitis vinifera L.) cDNA encoding for the enzyme stilbene synthase (StSy), under the control of the fruit-specific promoter TomLoxB. The resulting LoxS transgenic plants accumulated trans-resveratrol and trans-piceid, in particular in the skin of the mature fruits. Quantitative analyses carried out on LoxS fruits were compared with those of a tomato line constitutively expressing the stsy gene (35SS). The LoxS fruits contained levels of trans-resveratrol that were 20-fold lower than those previously reported for the 35SS line. The total antioxidant capability and ascorbate content in transformed fruits were also evaluated, and a significant increase in both was found in the LoxS and 35SS lines. These results could explain the higher capability of transgenic fruits to counteract the pro-inflammatory effects of phorbol ester in monocyte-macrophages via the inhibition of induced cyclo-oxygenase-2 enzyme.

Reversed-phase high-performance liquid chromatography (RP-HPLC) with photodiode array (PDA) and mass spectrometry (MS) detection was employed to study the accumulation of stilbenes and other naturally occurring polyphenol intermediates of flavonoid pathway in tomato fruits of plants genetically modified to synthesize resveratrol. The transgenic tomato fruits were obtained by overexpression of a grapevine gene encoding the enzyme stilbene synthase in tomato plants (Lycopersicon esculentum Mill.). Stilbenes and flavonoids, either glycosylated or free, were simultaneosly identified by electrospray interface (ESI)-MS in negative ionization mode and were quantified by PDA detection at the wavelength corresponding to their maximum absorbance. The two detectors were coupled online with an HPLC system utilizing a narrow-bore C18 reversed-phase column, which was eluted by a multistep gradient of increasing concentration of acetonitrile in water containing 0.5% (v/v) formic acid. The results of these analysis revealed that the genetic modification of the tomato plants originated different levels of accumulation of four stilbenes (i.e., trans- and cis-piceid and trans- and cis-resveratrol) in their fruit depending on the stages of ripening. Either at immature or at mature stages of ripening the stilbenes were preferentially accumulated in the fruit peel as the glycosylated form. The highest amount of trans-piceid and trans-resveratrol were found in the peel of fruits harvested at mature stage of ripening. The variations in the levels of rutin, naringenin, and chlorogenic acid found in the samples extracted from the fruits of transgenic tomato plants, in comparison to that determined in the control lines, seemed to be related to the genetic transformation, whose effect on the flavonoid biosynthetic pathway needs to be elucidated by additional studies.