Resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) (RSV) is a natural polyphenol with protective effects over cardiac tissues and can affect cell survival and differentiation in cardiac stem cells <em>trans</em>plantation. However, whether this agent can affect cardiomyocytes (CMs) differentiation of induced pluripotent stem cells (iPSCs) is not yet clear. This study explored whether RSV can affect CMs differentiation of human iPSCs. Under embryoid bodies (EBs) condition, the effect of RSV on the change of pluripotent markers, endoderm markers, mesoderm markers, and ectoderm markers was measured using qRT-PCR. Under CM differentiation culture, the effect of RSV on CM specific markers was also measured. The regulative role of RSV over canonical Wnt signal pathway and serum response factor- (SRF-) miR-1 axis and the functions of these two axes were further studied. Results showed that RSV had no effect on the self-renewal of human iPSCs but could promote mesoderm differentiation. Under CM differentiation culture, RSV could promote CM differentiation of human iPSCs through suppressing canonical Wnt signal pathway and enhancing SRF-miR-1 axis.

A sensitive and simple HPLC method has been developed and validated for the determination of oxyresveratrol (<em>trans</em>-2,4,3',5'-tetrahydroxystilbene, OXY) and resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>, RES) in rat plasma. The plasma samples were extracted with ethyl acetate and analyzed using HPLC on an Aglient Zorbax SB-C(18) column (250 x 4.6 mm, 5 microm) at a wavelength 320 nm, with a linear gradient of (A) acetonitrile and (B) 0.5% aqueous acetic acid (v/v), at a flow rate of 1.0 mL/min. The method was linear over the range of 0.1265-25.3 microg/mL for OXY and 0.117-23.4 microg/mL for RES. The extraction recovery for OXY, RES and internal standard ranged from 71.1 to 88.3%. The intra- and inter-day precisions were better than 10%, and the accuracy ranged from 89 to 108%. The validated method was used to study the pharmacokinetic profiles of OXY and RES in rat plasma after oral administration of Smilax china root extract.

Resveratrol (<em>3,5,4</em>'-<em>trans</em>-<em>trihydroxystilbene</em>) is a naturally occurring phytoalexin that is found in medicinal plants, grape skin, peanuts and red wine. Resveratrol exhibits a remarkable range of biological activities, including anticancer activity, antitubulin activity, anti-cardiovascular disease activity, etc. Several other natural products are structurally similar to resveratrol and also present in food. In addition, a series of resveratrol derivatives have been synthesized by the addition of defined functional groups to increase the potency or enhance the activity of specific properties of resveratrol. These resveratrol derivatives might provide promising functions as cardiovascular disease chemopreventive agents. In this review, we will attempt to summarize the main developments of resveratrol derivatives in cardiovascular disease and the main developments have occurred in derivatives of resveratrol's structure-activity relationship and cardiovascular disease over the last couple of decades.

Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of <em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>-4'-O-beta-D-glucopyranoside (compound 1) and (+)catechin (compound 2) from Rheum tanguticum Maxim. ex Balf. by stepwise elution with a pair of two-phase solvent system composed of ethyl acetate-ethanol-water (25:1:25, v/v) and (5:1:5, v/v), and stepwise increasing the flow-rate of the mobile phase from 0.8 to 2.0 mlmin(-1) after 5 h. The preparative HSCCC separation was performed on 250 mg of crude extract yielding pure compound 1 (10.2 mg) and compound 2 (26.7 mg) all at purities of over 96% in a single run. The structures of the two compounds have been elucidated by means of spectroscopic methods including MS and 1H, 13C nuclear magnetic resonance spectroscopy.

A novel ultra-performance LC-photodiode array-el-ESI-MS/MS screening method was developed for the detection and identification of natural antioxidants from radix et rhizoma Rhei. Nine compounds were found to possess a potential antioxidant activity, and their free radical-scavenging capacities were investigated in detail. The nine compounds were identified as 1-O-galloyl-2-O-cinnamoylglucose, 6-hydroxymusizin-8-O-β-D-glucopyranoside, (+)-catechin, gallic acid 3-O-β-D-glucopyranoside, <em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>- 4'-O-β-D-(2"-O-galloyl)-glucopyranoside, sennoside A, 4-(4'-hydroxyphenyl)-2- butanone-4'-O-β-D-(2"-O-galloyl-6"-O-p-coumaroyl) glucopyranoside, emodin-8-O-(6'-Omalonyl) glucopyranoside, and physcion-8-O-β-D-glucopyranoside. The reactivity and SC(50) values of those compounds were investigated, respectively. 1-O-Galloyl-2-O-cinnamoylglucose showed the strongest capability for scavenging 1,1-diphenyl-2-picrylhydrazylfree radical; <em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>-4'-O-β-D-(2"-O-galloyl) glucopyranoside showed the strongest capability for scavenging superoxide radical; 4-(4'-hydroxyphenyl)-2-butanone- 4'-O-2-D-(2"-O-galloyl-6"-O-p-coumaroyl) glucopyranoside exhibited the highest reactivity in the lipid peroxidation processes. The use of the analytical screening method based on ultra-performance LC-photodiode array-el-ESI-MS/MS would provide a new way for rapid detection of radical-scavenging natural compounds from radix et rhizoma Rhei or complex matrices.

Background: Isorhapontigenin (<em>trans</em>-<em>3,5,4</em>'-trihydroxy-3'-methoxystilbene, ISO), a dietary resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) derivative, possesses various health-promoting activities. To further evaluate its medicinal potentials, the pharmacokinetic and metabolomic profiles of ISO were examined in Sprague-Dawley rats. Methods: The plasma pharmacokinetics and metabolomics were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS), respectively. Results: Upon intravenous injection (90 μmol/kg), ISO exhibited a fairly rapid clearance (CL) and short mean residence time (MRT). After a single oral administration (100 μmol/kg), ISO was rapidly absorbed and showed a long residence in the systemic circulation. Dose escalation to 200 μmol/kg resulted in higher dose-normalized maximal plasma concentrations (Cmax/Dose), dose-normalized plasma exposures (AUC/Dose), and oral bioavailability (F). One-week repeated daily dosing of ISO did not alter its major oral pharmacokinetic parameters. Pharmacokinetic comparisons clearly indicated that ISO displayed pharmacokinetic profiles superior to resveratrol as its Cmax/Dose, AUC/Dose, and F were approximately two to three folds greater than resveratrol. Metabolomic investigation revealed that 1-week ISO administration significantly reduced plasma concentrations of arachidonic acid, cholesterol, fructose, allantoin, and cadaverine but increased tryptamine levels, indicating its impact on metabolic pathways related to health-promoting effects. Conclusion: ISO displayed favorable pharmacokinetic profiles and may be a promising nutraceutical in view of its health-promoting properties.

In the course of screening neuraminidase inhibitors from herbal medicines, Reynoutria elliptica exhibited high inhibitory activity. Four active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification using sillica gel, Sephadex LH-20 chromatography, and recrystallization. The chemical structures of these compounds were identified as 1,3,8-trihydroxy-6-methylanthraquinone (emodin) 1,8-dihydroxy-3-methoxy-6-methylanthraquinone (emodin 3-methyl ether; physcion), 1,3,8-trihydroxy-6-hydoxymethylanthraquinone (omega-hydroxyemodin), and <em>3,5,4</em>'-<em>trihydroxystilbene</em> (<em>trans</em>-resvertrol) by spectral data including MS, 1H-, and 13C-NMR. The IC50 values of emodin, emodin 3-methyl ether, omega-hydroxyemodin, and <em>trans</em>-resvertrol were 2.81, 74.07, 10.49, and 8.77 microM, respectively. They did not inhibit other glycosidase such as glucosidase, mannosidase, and galactosidase, indicating that they were relatively specific inhibitors of neuraminidase.

This article deals with the identification and characterization of process-related impurities of <em>trans</em>-resveratrol (<em>3,5,4</em>'-<em>trihydroxystilbene</em>), which exhibits several health benefits, including cancer prevention. During the synthesis of the bulk drug resveratrol, three new impurities were observed. The impurities were detected using the high-performance liquid chromatographic (HPLC) method, whose area percentages ranged from 0.05 to 0.3%. A systematic study was carried out to characterize them. These impurities were isolated by preparative HPLC and characterized by spectral data, subjected to co-injection in HPLC, and were found to be matching with the impurities present in the sample. LC-MS was performed to identify the mass of these impurities. Based on their spectral data (IR, NMR, and Mass), these impurities were characterized as 2-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol [Impurity-B], 3-(benzyloxy)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenol [Impurity-C], 5-{(E)-2-[4-(benzyloxy)phenyl]ethenyl}benzene-1,3-diol [Impurity-D). These compounds are not reported earlier as process-related impurities.

Resveratrol (<em>3,5,4</em>'-<em>trihydroxystilbene</em>) and piceatannol (3,4,3',5'-tetrahydroxy-<em>trans</em>-stilbene) are phytoalexins present in red grapes and wines. In vitro studies have revealed that piceatannol blocks LMP2A, a viral protein-tyrosine kinase implicated in leukemia, non-Hodgkin's lymphoma and other diseases associated with the Epstein-Barr virus, and has an antimelanoma effect on human melanoma cells. Resveratrol has several beneficial effects on human health, such as anticancer, cardioprotection, antioxidant, inhibition of platelet aggregation and anti-inflammatory activity. In this investigation, the collisional behaviour of deprotonated resveratrol and piceatannol obtained under electrospray conditions is described. The mechanisms involved in the fragmentation pattern of [M-H](-) species of the two compounds were investigated by performing MS(n) experiments, deuterium labelling and accurate mass measurements.

In response to the demand for new multifunctional materials characterized by high biocompatibility, hydrogel (HG) nanocomposites as a platform for bioactive compound delivery have been developed and fabricated. A specific crosslinking/copolymerization chemistry was used to construct hydrogels with a controlled network organization. The hydrogels were prepared using 3,6-anhydro-α-l-galacto-β-d-galactan (galactose hydrogel) together with resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) and calcium hydroxyapatite nanoparticles. The resveratrol was introduced in three different concentrations of 0.1, 0.5, and 1 mM. Nanosized calcium hydroxyapatite was synthesized by a microwave-assisted hydrothermal technique, annealed at 500 °C for 3 h, and introduced at a concentration 10% (<i>m</i>/<i>v</i>). The morphology and structural properties of Ca₁₀(PO₄)₆(OH)₂ and its composite were determined by using XRPD (X-ray powder diffraction) techniques, as well as the absorption and IR (infrared) spectroscopy. The average nanoparticle size was 35 nm. The water affinity, morphology, organic compound release profile, and cytocompatibility of the obtained materials were studied in detail. The designed hydrogels were shown to be materials of biological relevance and of great pharmacological potential as carriers for bioactive compound delivery. Their cytocompatibility was tested using a model of human multipotent stromal cells isolated from adipose tissue (hASCs). The biomaterials increased the proliferative activity and viability of hASCs, as well as reduced markers of oxidative stress. In light of the obtained results, it has been thought that the designed materials meet the requirements of the tissue engineering triad, and may find application in regenerative medicine, especially for personalized therapies.

Lysophosphatidic acid (LPA) has been known to induce epithelial-mesenchymal <em>trans</em>ition (EMT) to stimulate cancer cell invasion, and resveratrol (<em>3,5,4</em>'-<em>trans</em>-<em>trihydroxystilbene</em>; REV) suppresses the invasion and metastasis of various cancers. The current study aimed to identify the underlying mechanism by which LPA aggravates breast cancer cell invasion and the reversal of this phenomenon. Immunoblotting and quantitative RT-PCR analysis revealed that LPA induces amphiregulin (AREG) expression. Silencing of Y-box binding protein 1 (YB-1) or enhancer of zeste homolog 2 (EZH2) expression efficiently inhibited LPA-induced AREG expression. In addition, <em>trans</em>fection of the cells with YB-1 siRNA abrogated LPA-induced EZH2 and AREG expression, leading to attenuation of breast cancer cell invasion. Furthermore, we observed that both REV and 5-fluorouracil (5-Fu) significantly reduce LPA-induced YB-1 phosphorylation and subsequent breast cancer invasion. Importantly, combined treatment of REV with 5-Fu showed more significant inhibition of LPA-induced breast cancer invasion compared to single treatment. Therefore, our data demonstrate that the YB-1/EZH2 signaling axis mediates LPA-induced AREG expression and breast cancer cell invasion and its inhibition by REV and 5-Fu, providing potential therapeutic targets and inhibition of breast cancer.

Resveratrol, <em>trans</em> <em>3,5,4</em>'-<em>trihydroxystilbene</em>, is a stilbenoid polyphenol with a wide range of properties including antioxidant, neuroprotective, cardioprotective, anti-inflammatory and anticancer activities. It is found in the skins of grape (50-100 μg/ml), red wine, peanuts, bilberries, blueberries and cranberries. The most important effects of resveratrol have been found in cardiovascular disease, with pulmonary arterial hypertension (PAH) being a major severe and progressive component. Many factors are involved in the pathogenesis of PAH, including enzymes, <em>trans</em>cription factors, proteins, chemokines, cytokines, hypoxia, oxidative stress and others. Resveratrol treats PAH through its actions on various signaling pathways. These signaling pathways are mainly suppressed SphK1-mediated NF-κB activation, BMP/SMAD signaling pathway, miR-638 and NR4A3/cyclin D1 pathway, SIRT1 pathway, Nrf-2, HIF-1 α expression, MAPK/ERK1 and PI3K/AKT pathways, and RhoA-ROCK signaling pathway. Resveratrol efficiently inhibits the proliferation of pulmonary arterial smooth muscle cells and right ventricular remodeling, which are underlying processes leading to enhanced PAH. While supportive evidence from randomized controlled trials is yet to be available, current in vitro and in vivo studies seem to be convincing and suggest a therapeutic promise for the use of resveratrol in PAH.

Keywords: pulmonary arterial hypertension; resveratrol; signaling pathway.

Oxyresveratrol (<em>trans</em>-2,4,3',5'-tetrahydroxystilbene, OXY) and resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>, RES) are the two most important constituents of the traditional Chinese medicine Smilax china. A reversed-phase high-performance liquid chromatographic method was developed to determine OXY and RES in rat bile and urine after oral administration of Smilax china extract. The biological samples were analyzed by HPLC on Aglient Zorbax SB-C18 column (250 x 4.6 mm, 5 microm) at a wavelength 320 nm and at a flow rate of 1.0 mL/min. The method was accurate and reproducible for determination. The cumulative excretion of OXY and RES was 0.29% and 0.97% in bile samples, 0.84% and 0.65% in urine samples, respectively.

OBJECTIVE

The effects of estrogen replacement therapy, selective estrogen receptor modulators, or tibolone on vaginal squamous cell maturation in postmenopausal women are not well established. Resveratrol (<em>3,5,4</em>'-<em>trans</em>-<em>trihydroxystilbene</em>) has been shown to bind the estrogen receptor in rat uteri. The aim of this study was to cytologically evaluate vaginal smears from ovariectomized rats treated with resveratrol, raloxifene, tibolone and conjugated equine estrogen, and to compare each drug with regard to vaginal epithelial maturation.

METHODS

Forty-two bilaterally ovariectomized Wistar albino rats were equally randomized into 6 groups: (1) control sham-operated rats; (2) ovariectomized rats administered 0.1% ethanol; (3) ovariectomized rats administered resveratrol at a dose of 5 mg/kg/day p.o.; (4) ovariectomized rats administered conjugated equine estrogen (CEE) at a dose of 0.1 mg/kg/day p.o.; (5) ovariectomized rats administered tibolone at a dose of 0.25 mg/kg/day p.o., and (6) ovariectomized rats administered raloxifen at a dose of 1 mg/kg/day p.o. Administration of drugs started 5 days after bilateral ovariectomy and continued for 35 days. After 35 days of treatment a vaginal smear was obtained from each rat. Smears were stained with the usual Papanicolaou method, and observed with a light microscope by an experienced cytopathologist. Cytological grading was made according to the extent of parabasal, intermediate, superficial and anuclear squamous cells.

RESULTS

Ovariectomized rats had lower scores for superficial and anuclear cells when compared to sham-operated rats (p < 0.05). The CEE group had higher scores for superficial and anuclear cells than those of the ovariectomized, raloxifene and tibolone groups (p < 0.05). The resveratrol-treated rats had higher scores for superficial cells but lower scores for parabasal cells than ovariectomized rats (p < 0.05). The raloxifene and tibolone groups had the same scores for intermediate, superficial and anuclear cells but lower scores for parabasal cells compared to ovariectomized rats.

CONCLUSIONS

The results of our study suggest that resveratrol offsets the reduction in vaginal stratification generally observed after oophorectomy.

Resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>), a polyphenol found in red wine, has multiple beneficial activities that are similar to caloric restriction. In this study, we analyzed the effect of resveratrol on the gonadotropin genes, follicle-stimulating hormone (FSHβ) and luteinizing hormone (LHβ) in LβT2 immortalized mouse gonadotrope cells. Resveratrol specifically inhibited activin-induced FSHβ mRNA and protein expression, and reduced activin-stimulated Smad2/3 phosphorylation. Knockdown of SirT1 gene expression or SirT1 inhibition did not block repression of FSHβ expression or suppression of Smad2/3 phosphorylation, but did increase p53 acetylation. Taken together, our results suggest that resveratrol down-regulates Smad2/3 phosphorylation and suppresses FSHβ expression via a SirT1-independent pathway.

OBJECTIVE

The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, <em>3,5,4</em>'-<em>trans</em>-<em>trihydroxystilbene</em>) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle.

METHODS

Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week.

RESULTS

After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats.

CONCLUSIONS

The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

Pinostilbene (3-methoxyresveratrol or <em>trans</em>-3,4'-dihydroxy-5-methoxystilbene) is a naturally occurring monomethylether analogue of resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) that exhibits various pharmacological activities. To further examine its medicinal potential, a sensitive LC-MS/MS method was developed and validated for the determination of pinostilbene in rat plasma. Heavy Isotope labelled resveratrol was used as an internal standard. The ESI was operated in its negative ion mode while pinostilbene and resveratrol were measured by multiple reaction monitoring (MRM) using precursor-to-product ion <em>trans</em>itions of m/z 241→181 and m/z 233→191, respectively. This LC-MS/MS method had excellent selectivity, sensitivity (LLOQ=1ng/ml), accuracy (both intra- and interday analytical recovery within 100±15%) and precision (both intra- and interday RSD < 15%). The matrix effect was insignificant. The pharmacokinetics of pinostilbene was subsequently profiled in Sprague-Dawley rats. Upon intravenous administration (5 or 10mg/kg), pinostilbene displayed rapid clearance (Cl=129±42 or 107±31ml/min/kg) and extremely short mean <em>trans</em>it time (MTT=6.24±0.41 or 8.52±1.38min). After oral dosing (50mg/kg), the bioavailability of pinostilbene was limited but highly erratic (F=1.87±2.67%). Pharmacokinetic comparison among pinostilbene, resveratrol and some resveratrol analogues suggested that stilbenes with meta-hydroxyl group(s) may be associated with metabolic instability and subsequently suffer from rapid clearance and low oral bioavailability. The information obtained from this study will facilitate further exploration on pinostilbene as well as other resveratrol analogues.

<em>trans</em>-Resveratrol (<em>3,5,4</em>'-<em>trihydroxystilbene</em>) is a natural polyphenolic compound that exhibits antioxidant properties. Our study aimed at studying the HO*-induced oxidation of resveratrol (100 micromol.L(-1)) in aerated aqueous solutions. Gamma radiolysis of water was used to generate HO*/O(2)(*-) free radicals (I = 10 Gy.min(-1), dose = 400 Gy). Oxidation products were identified by direct infusion mass spectrometry and high-performance liquid chromatography/mass spectrometry. For each product, structural elucidation was based on simple mass spectra, fragmentation spectra and deuterium/hydrogen exchange spectra; the comparison with mass spectra of synthetic products provided valuable information allowing the complete identification of the oxidation products. Four products resulting from the direct attack of HO* radicals towards resveratrol were identified respectively as piceatannol (<em>trans</em>-3,5,3',4'-tetrahydroxystilbene), 3,5-dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde.

BACKGROUND

Compounds based on <em>trans</em>-1,2-diphenylethene are the subject of intense interest both for their optical properties and as potential leads for drug discovery, as a consequence of their anticancer, anti-inflammatory and antioxidant properties. Perhaps the best known of these is <em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em> (resveratrol), that has been identified as a promising lead in the search for anti-ageing therapeutics.

RESULTS

We report here a new, convenient, one-pot stereo-selective synthesis of resveratrol and other trans-stilbene derivatives. A wide range of known and novel "Resveralogues" were synthesised by using this simple protocol, including examples with electron donating and electron withdrawing substituents, in uniformly high yield. The structures of all compounds were confirmed by standard methods including (1)H and (13)C NMR, IR and High Resolution Mass spectroscopy.

CONCLUSIONS

We have established a simple and convenient protocol for resveralogue synthesis. It is readily scalable, and sufficiently robust and simple for ready use in automated synthesis or for library development of resveralogues. This supersedes previously reported synthetic methods that required inert conditions, extensive purification and/or costly reagents. Graphical abstractOne-pot preparation of diverse Resveralogues - high yields of product with minimal purification.

Resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) is a phytoalexin found in diverse plant species, including grapes and peanuts. The antioxidant, anticancer, and cardioprotective properties of resveratrol have been well-characterized. The anti-obesity effect of resveratrol has also been demonstrated in previous studies. In this study, we evaluated the effects of a resveratrol analogue, (E)-1,2-di(3,5-dimethoxyphenyl)ethene, on adipocyte differentiation using 3T3-L1 cells. According to our results, the tested analogue potently inhibits the differentiation of 3T3-L1 adipocyte to a greater degree than resveratrol. Moreover, (E)-1,2-di(3,5-dimethoxyphenyl)ethene strongly downregulated the expression of fatty acid metabolism-related proteins such as fatty acid synthase and acetyl-CoA carboxylase. These results point to the potential of (E)-1,2-di(3,5-dimethoxyphenyl)ethene as an obesity prevention agent.

From the underground parts of Eskemukerjea megacarpum HARA, two new stilbenes (14, 15) were isolated, together with a known coumarin, 5,7-dihydroxycoumarin (1), a tyramine derivative, <em>trans</em>-feruloyltyramine (2), two pyrogallol derivatives, gallic acid (3) and beta-glucogallin (4), four flavonoids, trifolin (5), hyperin (6), myricetin 3-O-beta-D-galactopyranoside (7), and myricitrin (8), five stilbenes, resveratorol (9), astringenin (10), piceid (11) astringin (12), and resveratorol 3-O-beta-D-(6-O-galloyl)glucopyranoside (13), a flavan-3-ol, (-)-epigallocatechin 3-O-gallate (16), two proanthocyanidins, catechin-(4alpha-->8)-epigallocatechin 3-O-gallate (17) and epicatechin 3-O-gallate-(4beta-->8)-epigallocatechin 3-O-gallate (18), and an anthocyanin, idaein (19). Compounds 14 and 15 were identified as (E)-3,5,3',4'-tetrahydroxystilbene 3-O-beta-D-(6-O-galloyl)glucopyranoside and (E)-<em>3,5,4</em>'-<em>trihydroxystilbene</em> 3-O-beta-D-(6-O-galloyl)glucopyranoside, respectively, based on spectral and chemical data.

Resveratrol (<em>3,5,4</em>'-<em>trihydroxystilbene</em>) is one of the most abundant polyphenols in red grapes, and red wine represents one of the most important dietary source of this compound. Although its beneficial properties on human health have been widely investigated over the last 30 years, very little is known about its derivatives. Resveratrol can indeed undergo glycosylation, oligomerization and, upon UV-light exposure, it can isomerize from the <em>trans</em>- to the cis-isomer, which can further cyclize to 2,4,6-trihydroxyphenanthrene (THP). Although the effects of THP on human health are not yet known, being a polycyclic aromatic hydrocarbon, it can be potentially harmful. Since no data about THP occurrence in plant food and beverages are available, a simple procedure based on liquid-liquid extraction and GC-MS has been developed and validated for the simultaneous qualitative and quantitative analysis of <em>trans</em>-resveratrol, cis-resveratrol and THP in red wine, before and after UV-light exposure.

Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (<em>trans</em>-<em>3,5,4</em>'-<em>trihydroxystilbene</em>) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies might be gleaned using publicly available databases. A web-based microarray gene expression data-mining platform, Oncomine, was selected and used to determine whether QR2 may serve as a mechanistic and functional biotarget within the various CRC etiologies. We found that QR2 messenger RNA (mRNA) is overexpressed in CRC characterized by CIN, particularly in cells showing a positive KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation, as well as by the MSI but not the CIMP phenotype. Mining of Oncomine revealed an excellent correlation between QR2 mRNA expression and certain CRC etiologies. Two resveratrol-associated genes, adenomatous polyposis coli (APC) and TP53, found in CRC were further mined, using cBio portal and Colorectal Cancer Atlas which predicted a mechanistic link to exist between resveratrol→QR2/TP53→CIN. Multiple web-based data mining can provide valuable insights which may lead to hypotheses serving to guide clinical trials and design of therapies for enhanced disease prognosis and patient survival. This approach resembles a BioGPS, a capability for mining web-based databases that can elucidate the potential links between compounds to provide correlations of these interactions with specific diseases.

Liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization has been successfully applied to the determination of <em>trans</em>-resveratrol (<em>3,5,4</em>'-<em>trihydroxystilbene</em>) in wine. Of a range of analytical conditions that were tested, optimum results were obtained by the use of reversed-phase high performance liquid chromatography (HPLC) using a mixture of methanol and ammonium acetate as the mobile phase. The negative-ion spectrum of <em>trans</em>-resveratrol showed pseudo-molecular ion, [M - H](-), which was the most abundant ion, and low fragment ions corresponding to the losses of hydroxyl groups of the phenol nucleus. Enhanced selectivity for the separation between <em>trans</em>-resveratrol and endogenous wine constituents was afforded by sample purification with a tandem solid-phase extraction method. The approach permits detection at low concentration of <em>trans</em>-resveratrol. The combination of improved sample pretreatment and an isocratic chromatographic system in conjunction with internal standardization forms the basis of a new assay for the quantitation of <em>trans</em>-resveratrol in wine. Full-scan mass spectra were readily obtained from 8 ng of <em>trans</em>-resveratrol, while a limit of detection of 200 pg (signal-to-noise ratio 3) was attained in the selected ion monitoring mode. The application of LC/MS to the determination of <em>trans</em>-resveratrol in wines is demonstrated by the analysis of red wines. Copyright 1999 John Wiley & Sons, Ltd.