Search Results (47)

Saffron (Crocus sativus L.) contains bioactive compounds with potential health benefits, including modulation of protein function and gene expression. However, their ability to tune the epigenetic machine remains poorly understood. This study employs molecular docking (AutoDock Vina 1.4), dynamics simulations, and MM/PBSA calculations to investigate the interactions between four saffron-derived molecules—crocetin, beta-D-glucosyl trans-crocetin, picrocrocin and safranal—and four epigenetic enzymes—DNMT1, DNMT3a, HDAC2, and SIRT1. Our in silico screening identifies beta-D-glucosyl trans-crocetin, one of the saffron’s crocins, as a potential DNMT1 inhibitor. Along with crocetin, it also shows the ability to inhibit HDAC2 and activate SIRT1. Picrocrocin displays a resveratrol-like ability to activate SIRT1. None of the saffron-derived compounds effectively bind or inhibit DNMT3a. Among the tested molecules, safranal shows no interaction with the selected epigenetic targets. These findings highlight saffron’s nutriepigenomic potential and emphasize the need for functional validation within relevant in vitro and in vivo experimental methodologies. Full article

Resveratrol is one of the most extensively studied natural products due to its pleiotropic health benefits. However, its low water solubility and limited stability hinder its application in the nutraceutical, cosmetic, and pharmaceutical sectors. In this work, we investigated the ability of a cationic mono-choline-β-cyclodextrin derivative to complex trans-resveratrol. The complex was prepared using a phase solubility method without using organic solvents and was found to be stable after freeze-drying. The complex was characterized by a phase solubility study, NMR spectroscopy, and molecular modeling simulations, which revealed a 1:1 stoichiometry, a stability constant of 2051 M⁻¹ (K_C), and structural details. Complexation improved resveratrol’s solubility and dissolution rate, reduced its photoinduced trans-to-cis isomerization, and preserved its radical scavenging activity. The wound-healing activity of the complex was demonstrated via in vitro experiments on human keratinocyte cells. Full article

Resveratrol (trans-3,5,4′-trihydroxystilbene, RES) is one of the most well-known natural products with numerous health benefits. To explore the nutraceutical potentials of some dietary RES derivatives including isorhapontigenin (trans-3,5,4′-trihydroxy-3′-methoxystilbene, ISO), oxyresveratrol (trans-3,5,2′,4′-tetrahydroxystilbene, OXY) and pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene, PTS), their impacts on metabolism and health were assessed in Sprague Dawley rats after a two-week daily oral administration at the dose of 100 µmol/kg/day. Non-targeted metabolomic analyses were carried out with the liver, heart, brain and plasma samples using gas chromatography–tandem mass spectrometry (GC-MS/MS). Notable in vivo health benefits were observed, as the rats received ISO, PTS or RES showed less body weight gain; the rats received OXY or RES displayed healthier fasting blood glucose levels; while all of the tested stilbenes exhibited cholesterol-lowering effects. Additionally, many important metabolic pathways such as glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and fatty acid oxidation were found to be modulated by the tested stilbenes. Besides the reaffirmation of the well-known beneficial effects of RES in diabetes, obesity, cardiovascular disease and Alzheimer’s disease, the metabolomic analyses also suggest the anti-diabetic, cardio-, hepato- and neuro-protective activities of ISO; the anti-diabetic, cardio-, hepato- and neuro-protective effects of OXY; and the anti-aging, anti-inflammatory, cardio-, hepato- and neuro-protective potential of PTS. Interestingly, although these stilbenes share a similar structure, their biological activities appear to be distinct. In conclusion, similarly to RES, ISO, OXY and PTS have emerged as promising candidates for further nutraceutical development. Full article

The targeted compounds in this research, resveratrol analogs 1–14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC₅₀ values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes’ structure and identify the non-covalent interactions responsible for the complex’s stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized. Full article

From grape cultivation to ripening and harvest timing to processing, each step of the winemaking process can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using a co-inoculation winemaking technology. The main new idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35–40%) and quercetin (>35–40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has better aroma and stability due to the higher mannoprotein content, and (4) better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. This study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin. This study represents a small part of the investigation of the influence of non-Saccharomyces yeasts on the phenolic profile of wine, which still requires extensive research with practical application. In addition, non-Saccharomyces yeasts such as Kluyveromyces thermotolerans, Candida stellata, and Metschnikowia pulcherrima could also be used in future studies. Full article

Understanding the impact of pre-treatment methods on the phytochemical composition of grapes is essential for optimizing grape quality and producing raisins with desirable characteristics. Therefore, this study meticulously analyzed the impact of two distinct pre-treatment methods, oak ash and potassium carbonate (K₂CO₃), on the composition of essential phytochemical components in grapes. This research encompassed phenolic compounds, anthocyanins, phenolic acids, flavonoids, and phytoalexins. This study investigates the impact of pre-treatment methods, oak ash and K₂CO₃, on the phytochemical composition of grapes. Significant differences were observed in anthocyanins, flavonoids, phytoalexins, and phenolic acids between the treatments. Oak ash exhibited advantages in preserving specific compounds, including higher levels of anthocyanins, flavonols, flavones, flavanones, catechins, resveratrol, pterostilbene, and viniferin, compared to K₂CO₃. Notably, the delphinidin-3-O-glycoside content was significantly higher in the oak ash treatment. An analysis of phenolic compounds revealed distinctions in hydroxycinnamic acids, hydroxybenzoic acids, benzaldehyde, and phenylacetaldehyde. Additionally, gallic acid, vanillic acid, trans-caffeic acid, trans-p-coumaric acid, and (-)-epicatechin were significantly more prevalent in the K₂CO₃ treatment, while ferulic acid and quercetin were more prevalent in the oak ash treatment. These findings underscore the pivotal role of pre-treatment methods in shaping the phytochemical content of grapes, thus holding critical implications for grape-derived products’ quality and potential health benefits. Full article

A grapevine shoot extract (GSE) was obtained using ultrasound-assisted extraction and characterized. The main phenolic constituents were identified as stilbenoids. Among them, trans-resveratrol and trans-ε-viniferin stood out. The GSE was administered to an isoproterenol-induced myocardial injury animal model. The extract alleviated the associated symptoms of the administration of the drug, i.e., the plasma lipid profile was improved, while the disturbed plasma ion concentration, the cardiac dysfunction markers, the DNA laddering, and the necrosis of myocardial tissue were diminished. This effect could be related to the anti-oxidative potential of GSE associated with its antioxidant properties, the increased levels of endogenous antioxidants (glutathione and enzymatic antioxidants), and the diminished lipid peroxidative markers in the heart. The results also revealed angiotensin-converting enzyme (ACE)-inhibitory activity, which indicated the potential of GSE to deal with cardiovascular disease events. This work suggests that not only trans-resveratrol has a protective role in heart function but also GSE containing this biomolecule and derivatives. Therefore, GSE has the potential to be utilized in the creation of innovative functional ingredients. Full article

Previously, we showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) ligand and a potent and persistent toxicant and carcinogenic agent, induces high levels of murine myeloid-derived suppressor cell (MDSC) when injected into mice. In the current study, we demonstrate that Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV), an AhR antagonist, reduces TCDD-mediated MDSC induction. RSV decreased the number of MDSCs induced by TCDD in mice but also mitigated the immunosuppressive function of TCDD-induced MDSCs. TCDD caused a decrease in F4/80+ macrophages and an increase in CD11C+ dendritic cells, while RSV reversed these effects. TCDD caused upregulation in CXCR2, a critical molecule involved in TCDD-mediated induction of MDSCs, and Arginase-1 (ARG-1), involved in the immunosuppressive functions of MDSCs, while RSV reversed this effect. Transcriptome analysis of Gr1⁺ MDSCs showed an increased gene expression profile involved in the metabolic pathways in mice exposed to TCDD while RSV-treated mice showed a decrease in such pathways. The bio-energetic profile of these cells showed that RSV treatment decreased the energetic demands induced by TCDD. Overall, the data demonstrated that RSV decreased TCDD-induced MDSC induction and function by altering the dynamics of various myeloid cell populations involving their numbers, phenotype, and immunosuppressive potency. Because MDSCs play a critical role in tumor growth and metastasis, our studies also support the potential use of RSV to attenuate the immunosuppressive properties of MDSC. Full article

The seeds of Paeonia clusii Stern subsp. clusii and Paeonia mascula (L.) Mill. subsp. mascula growing wild in Greece, though not previously investigated, has been studied as a source of bioactive stilbenoids and other phenolics. Their methanol extracts were analyzed using ultra high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS), and among the identified metabolites (62), 19 paeoniflorin’s derivatives, 17 flavonoids and 12 stilbenes were detected. Moreover, through classic phytochemical separation procedures, twelve among them were isolated and fully spectrally determined as trans-resveratrol, trans-resveratrol-4′-O-β-D-glucopyranoside, cis-resveratrol-4′-O-β-D-glucopyranoside, trans-gnetin-H, trans-ε-viniferin, luteolin, luteolin-3′-O-β-D-glucopyranoside, luteolin-3′,4′-di-O-β-D-glucopyranoside, apigenin, hispidulin, paeoniflorin and benzoyl-paeoniflorin. All seed extracts were measured for their total phenolic content (TPC), appearing as a rich source (116.04 and 103.63 mg GAE/g extract, respectively), followed by free radical (DPPH) scavenging capacity (75.24% and 91.54% inhibition at the concentration of 200 μg/mL). The evaluation of tyrosinase inhibition for both extracts (61% and 70%, respectively) confirmed the potential for their future application in skin health care, comparable with other paeonies of Chinese origin, which are well-known as skin whitening and anti-aging promoters. Full article

The BRS Carmem grape was developed as an alternative for processing juices and wines. This study aimed to determine the phenolic compounds (PC) in the edible parts of this grape from two harvests—one harvested at ideal maturation time and another when the grapes were still immature—using HPLC-DAD-ESI-MS/MS. Student’s t-test was used (α = 0.05) to evaluate differences in the PC content between the edible parts and between the harvests. Both skins showed a predominance of flavonols, anthocyanins, hydroxycinnamic acids derivatives (HCAD) and stilbenes, with higher concentrations for harvest 1 than harvest 2. For both harvests (harvest 1 and harvest 2), the HCAD (mg of caftaric acid•kg fruit⁻¹) was higher in whole grapes (383.98 and 67.09) than in their skins (173.95 and 21.74), with a predominance of trans-caffeic acid for all samples; the flavan-3-ols and proanthocyanidins (mg of (+)-catechin•kg fruit⁻¹) presented higher concentrations in the seeds (flavan-3-ols: 203.20 and 182.71, proanthocyanidins: 453.57 and 299.86) than in the skins (flavan-3-ols: 1.90 and 4.56, proanthocyanidins: 37.58 and 98.92); the stilbenes concentration (µg 3-glc-resveratrol•kg fruit⁻¹) was higher for the seeds from harvest 2 (896.25) than those from harvest 1 (48.67). BRS Carmem grapes contain a phenolic composition complex, and still have a relevant concentration of flavonols, anthocyanins and stilbenes, even when immature. Full article

This review refers to botanical, ecological and phytochemical characteristics of Vitis vinifera L. (vine grape)–a species, the valuable properties of which are widely exploited in the food industry and in recent times in medicine as well as in phytocosmetology. The general characteristic of V. vinifera, followed by the chemical composition and biological activities of different extracts obtained from the plant (fruit, skin, pomace, seed, leaf and stem extracts), are provided. A concise review of the extraction conditions of grape metabolites and the methods of their analysis are also presented. The biological activity of V. vinifera is determined by the presence of high contents of polyphenols, mainly flavonoids (e.g., quercetin, kaempferol), catechin derivatives, anthocyanins and stilbenoids (e.g., trans-resveratrol, trans-ε-viniferin). The review pays particular attention to the application of V. vinifera in cosmetology. It has been proven that V. vinifera possesses strong cosmetological-related properties, such as anti-ageing properties, anti-inflammatory properties and skin-whitening properties. Moreover, a review of studies on V. vinifera biological activities, which are of particular interest for dermatologic problems, are disclosed. Furthermore, the work also emphasises the importance of biotechnological studies on V. vinifera. The last part of the review is addressed to the safety of the use of V. vinifera. Full article

In this study, the black fertile (BSs) and the red unfertile seeds (RSs) of the Greek endemic Paeonia clusii subsp. rhodia (Stearn) Tzanoud were studied for the first time. Nine phenolic derivatives, trans-resveratol, trans-resveratrol-4′-O-β-d-glucopyranoside, trans-ε-viniferin, trans-gnetin H, luteolin, luteolin 3′-O-β-d-glucoside, luteolin 3′,4′-di-O-β-d-glucopyranoside, and benzoic acid, along with the monoterpene glycoside paeoniflorin, have been isolated and structurally elucidated. Furthermore, 33 metabolites have been identified from BSs through UHPLC-HRMS, including 6 monoterpene glycosides of the paeoniflorin type with the characteristic cage-like terpenic skeleton found only in plants of the genus Paeonia, 6 gallic acid derivatives, 10 oligostilbene compounds, and 11 flavonoid derivatives. From the RSs, through HS-SPME and GC-MS, 19 metabolites were identified, among which nopinone, myrtanal, and cis-myrtanol have been reported only in peonies’ roots and flowers to date. The total phenolic content of both seed extracts (BS and RS) was extremely high (up to 289.97 mg GAE/g) and, moreover, they showed interesting antioxidative activity and anti-tyrosinase properties. The isolated compounds were also biologically evaluated. Especially in the case of trans-gnetin H, the expressed anti-tyrosinase activity was higher than that of kojic acid, which is a well-known whitening agent standard. Full article

Stilbenoids are anti-inflammatory and antioxidant compounds, with resveratrol being the most investigated molecule in this class. However, the actions of most other stilbenoids are much less studied. This study compares five monomeric (resveratrol, piceatannol, pterostilbene, pinostilbene, and trimethoxy-resveratrol) and two dimeric (dehydro-δ-viniferin and trans-δ-viniferin) stilbenoids for their capability to modulate the production of bacteria-induced cytokines (IL-12, IL-10, and TNF-α), as well as lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), in murine bone marrow-derived dendritic cells. All monomeric species showed dose-dependent inhibition of E. coli-induced IL-12 and TNF-α, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited L. acidophilus-induced IL-12, IL-10, and TNF-α production. The dimer dehydro-δ-viniferin remarkably enhanced L. acidophilus-induced IL-12 production. The contrasting effect of resveratrol and dehydro-δ-viniferin on IL-12 production was due, at least in part, to a divergent inactivation of the mitogen-activated protein kinases by the two stilbenoids. Despite having moderate to high total antioxidant activity, dehydro-δ-viniferin was a weak inhibitor of LPS-induced ROS formation. Conversely, resveratrol and piceatannol potently inhibited LPS-induced ROS formation. Methylated monomers showed a decreased antioxidant capacity compared to resveratrol, also depending on the methylation site. In summary, the immune-modulating effect of the stilbenoids depends on both specific structural features of tested compounds and the stimulating bacteria. Full article

Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol found in grapes, red wine, peanuts, and apples, has been reported to exhibit a wide range of biological and pharmacological properties. In addition, resveratrol has been reported to intervene in multiple stages of carcinogenesis. It has also been known to kill several human cancer cells through programmed cell death (PCD) mechanisms such as apoptosis, autophagy, and necroptosis. However, resveratrol has limitations in its use as an anticancer agent because it is susceptible to photoisomerization owing to its unstable double bond, short half-life, and is rapidly metabolized and eliminated. Trans-(E)-resveratrol is nontoxic, and has several biological and pharmacological activities. However, little is known about the pharmacological properties of the photoisomerized cis-(Z)-resveratrol. Therefore, many studies on resveratrol derivatives and analogues that can overcome the shortcomings of resveratrol and increase its anticancer activity are underway. This review comprehensively summarizes the literature related to resveratrol-induced PCD, such as apoptosis, autophagy, necroptosis, and the development status of synthetic resveratrol derivatives and analogues as novel anticancer drugs. Full article

Trans-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans-resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans-resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC₆(3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2′-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans-resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans-resveratrol. Full article