Suppression of virulence factors of uropathogenic Escherichia coli by Trans-resveratrol and design of nanoemulgel.

BACKGROUND: Development of multidrug resistance in Uropathogenic Escherichia coli (UPEC) makes treatment of Urinary Tract Infections (UTIs) a major challenge. This study was conducted to investigate the effect of trans-resveratrol (t-RSV) at a subinhibitory concentration (sub-MIC-t-RSV) on phenotypic and genotypic expression of virulence factors of clinical isolates of UPEC and develop a nanoformulation of t-RSV. Fifty-five clinical UPEC strains were investigated for the presence of virulence factors by phenotypic methods and PCR detection of virulence genes. The effect of sub-MIC-t-RSV was studied on the phenotypic and genotypic expression of virulence factors. t-RSV-loaded nanoemulgel formulation was prepared and characterized. RESULTS: Out of the 55 tested isolates, 50.9% were biofilm producers, 23.6% showed both mannose-sensitive and mannose-resistant hemagglutination, 21.8% were serum-resistant, 18.2% were hemolysin producers, while 36.4% showed cytotoxic effect on HEp-2 cells. A total of 25.5% of the isolates harbor one or more of hly-A, cnf-1 and papC genes, while 54.5% were positive for one or more of fimH, iss and BssS genes. A concentration of 100 µg/mL of t-RSV effectively downregulates the phenotypic and genotypic expression of the virulence factors in positive isolates. A stable t-RSV-nanaoemulgel with droplet size of 180.3 nm and Zetapotential of -46.9 mV was obtained. CONCLUSION: The study proves the effective role of t-RSV as an antivirulence agent against clinical UPEC isolates in vitro and develops a stable t-RSV-nanoemulgel formulation to be assessed in vivo. The promising antibacterial and antivirulence properties of t-RSV place this natural compound to be a better alternative in the treatment of persistent UTIs.

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence.

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.

Trans-resveratrol reduced hepatic oxidative stress in an animal model without inducing an upregulation of nuclear factor erythroid 2-related factor 2.

Trans-resveratrol, a widely used supplement for humans, aims to enhance the body's antioxidant defense. Studies suggest that it exerts anti-inflammatory and antioxidant effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2). In order to evaluate this hypothesis, LDLr(-/-) mice were fed a Western diet to induce liver inflammation and oxidative stress. One group was fed a diet containing 0.60 mg/day of trans-resveratrol (RESV), while another group received no dietary supplementation (CONT). Oxidative stress biomarkers and inflammatory cytokines were assessed in liver homogenates. It was observed that trans-resveratrol decreased hepatic oxidative stress by increasing the GSH/GSSG ratio and reducing malondialdehyde (MDA) concentration. However, the RESV group exhibited a reduction in Nrf2 relative expression compared to CONT. Additionally, trans-resveratrol supplementation reduced nuclear factor-κB (NF-κB) expression but led to an increase in IL-6, with no significant changes observed in tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations. Overall, these findings indicate that the in vivo antioxidant impact induced by trans-resveratrol supplementation in hepatic tissue did not correlate with increase of inflammatory cytokines and Nrf2 relative expression. Further exploration of alternative mechanisms, such as direct radical scavenger activity, is warranted to elucidate the antioxidant effect.

High-efficiency novel extraction process of target polyphenols using enzymes in hydroalcoholic media.

Agro-industrial by-products are a sustainable source of natural additives that can replace the synthetic ones in the food industry. Grape pomace is an abundant by-product that contains about 70% of the grape's polyphenols. Polyphenols are natural antioxidants with multiple health-promoting properties. They are secondary plant metabolites with a wide range of solubilities. Here, a novel extraction process of these compounds was developed using enzymes that specifically liberates target polyphenols in the appropriate hydroalcoholic mixture. Tannase, cellulase, and pectinase retained 22, 60, and 52% of their activity, respectively, in ethanol 30% v/v. Therefore, extractions were tested in ethanol concentrations between 0 and 30% v/v. Some of these enzymes presented synergistic effects in the extraction of specific polyphenols. Maximum yield of gallic acid was obtained using tannase and pectinase enzymes in ethanol 10% v/v (49.56 ± 0.01 mg L-1 h-1); in the case of p-coumaric acid, by cellulase and pectinase treatment in ethanol 30% v/v (7.72 ± 0.26 mg L-1 h-1), and in the case of trans-resveratrol, by pectinase treatment in ethanol 30% v/v (0.98 ± 0.04 mg L-1 h-1). Also, the effect of enzymes and solvent polarity was analysed for the extraction of malvidin-3-O-glucoside, syringic acid, and quercetin. Previous studies were mainly focused on the maximization of total polyphenols extraction yields, being the polyphenolic profile the consequence but not the driving force of the optimization. In the present study, the basis of a platform for a precise extraction of the desire polyphenols is provided. KEY POINTS: • Enzymes can be used up to ethanol 30% v/v. • The specific enzymes' action determines the polyphenolic profile of the extracts. • The yields obtained of target polyphenols are competitive.

Inhibition of ANO1 by Cis- and Trans-Resveratrol and Their Anticancer Activity in Human Prostate Cancer PC-3 Cells.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 µM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 µM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.

Selective Encapsulation of the Polyphenols on Silk Fibroin Nanoparticles: Optimization Approaches.

The present study proposes a method for designing small bioactive nanoparticles using silk fibroin as a carrier to deliver hydrophobic polyphenols. Quercetin and trans-resveratrol, widely distributed in vegetables and plants, are used here as model compounds with hydrophobic properties. Silk fibroin nanoparticles were prepared by desolvation method and using various concentrations of ethanol solutions. The optimization of the nanoparticle formation was achieved by applying Central Composite Design (CCD) and the response surface methodology (RSM). The effects of silk fibroin and ethanol solution concentrations together with the pH on the selective encapsulation of phenolic compounds from a mixture were reported. The obtained results showed that nanoparticles with an average particle size of 40 to 105 nm can be prepared. The optimized system for the selective encapsulation of the polyphenols on the silk fibroin substrate was determined to be 60% ethanol solution and 1 mg/mL silk fibroin concentration at neutral pH. The selective encapsulation of the polyphenols was achieved, with the best results being obtained in the case of resveratrol and quercetin and encapsulation of gallic and vanillic acids being rather poor. Thin-layer chromatography confirmed the selective encapsulation and the loaded silk fibroin nanoparticles exhibited antioxidant activity.

Resistance to Resveratrol Treatment in Experimental PTSD Is Associated with Abnormalities in Hepatic Metabolism of Glucocorticoids.

Glucocorticoids are metabolized by the CYP3A isoform of cytochrome P450 and by 11-ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1). Experimental data suggest that post-traumatic stress disorder (PTSD) is associated with an increase in hepatic 11ß-HSD-1 activity and a concomitant decrease in hepatic CYP3A activity. Trans-resveratrol, a natural polyphenol, has been extensively studied for its antipsychiatric properties. Recently, protective effects of trans-resveratrol were found in relation to PTSD. Treatment of PTSD rats with trans-resveratrol allowed the rats to be divided into two phenotypes. The first phenotype is treatment-sensitive rats (TSR), and the second phenotype is treatment-resistant rats (TRRs). In TSR rats, trans-resveratrol ameliorated anxiety-like behavior and reversed plasma corticosterone concentration abnormalities. In contrast, in TRR rats, trans-resveratrol aggravated anxiety-like behavior and decreased plasma corticosterone concentration. In TSR rats, hepatic 11ß-HSD-1 activity was suppressed, with a concomitant increase in CYP3A activity. In TRR rats, the activities of both enzymes were suppressed. Thus, the resistance of PTSD rats to trans-resveratrol treatment is associated with abnormalities in hepatic metabolism of glucocorticoids. The free energy of binding of resveratrol, cortisol, and corticosterone to the human CYP3A protein was determined using the molecular mechanics Poisson-Boltzmann surface area approach, indicating that resveratrol could affect CYP3A activity.

Characterization of Cell Death Induced by Imine Analogs of Trans-Resveratrol: Induction of Mitochondrial Dysfunction and Overproduction of Reactive Oxygen Species Leading to, or Not, Apoptosis without the Increase in the S-Phase of the Cell Cycle.

Trans-resveratrol (RSV) is a non-flavonoid polyphenol (stilbene) with numerous biological activities, such as anti-tumor activities. However, RSV is rapidly metabolized, which limits its therapeutic use. The availability of RSV analogues with similar activities for use in vivo is therefore a major challenge. For this purpose, several isomeric analogues of RSV, aza-stilbenes (AZA-ST 1a-g), were synthesized, and their toxicities were characterized and compared to those of RSV on murine N2a neuronal cells using especially flow cytometric methods. All AZA-ST 1a-g have an inhibitory concentration 50 (IC50) between 11.3 and 25 µM when determined by the crystal violet assay, while that of RSV is 14.5 µM. This led to the characterization of AZA-ST 1a-g-induced cell death, compared to RSV, using three concentrations encompassing the IC50s (6.25, 12.5 and 25 µM). For AZA-ST 1a-g and RSV, an increase in plasma membrane permeability to propidium iodide was observed, and the proportion of cells with depolarized mitochondria measured with DiOC6(3) was increased. An overproduction of reactive oxygen species (ROS) was also observed on whole cells and at the mitochondrial level using dihydroethidium and MitoSox Red, respectively. However, only RSV induced a mode of cell death by apoptosis associated with a marked increase in the proportion of cells with condensed and/or fragmented nuclei (12.5 µM: 22 ± 9%; 25 µM: 80 ± 10%) identified after staining with Hoechst 33342 and which are characteristic of apoptotic cells. With AZA-ST, a slight but significant increase in the percentage of apoptotic cells was only detected with AZA-ST 1b (25 µM: 17 ± 1%) and AZA-ST 1d (25 µM: 26 ± 4%). Furthermore, only RSV induced significant cell cycle modifications associated with an increase in the percentage of cells in the S phase. Thus, AZA-ST 1a-g-induced cell death is characterized by an alteration of the plasma membrane, an induction of mitochondrial depolarization (loss of ΔΨm), and an overproduction of ROS, which may or may not result in a weak induction of apoptosis without modification of the distribution of the cells in the different phases of the cell cycle.

Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies.

Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, ß-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 × 4.6 mm, 3 µ) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 > 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (-4 °C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ's bioanalysis and pharmacokinetic properties which is useful for future clinical trials.

Polyphenolic Compounds in Extracts from Roasted Grapevine Canes: An Investigation for a Circular Approach to Increase Sustainability in the Viticulture Sectors.

In this study, we compared the polyphenolic composition of the roasted grapevine wood chips of four Vitis vinifera cultivars-namely, Sorbara, Grasparossa, Malbo Gentile, and Spergola. These waste byproducts have the potential as infusion chips for the aging of alcoholic beverages and vinegars, contributing to an enriched sensory profile. Roasting amplifies aromatic nuances and triggers the depletion of crucial bioactive compounds, including polyphenols. We investigated the extent of polyphenolic loss in the ethanolic extract of roasted grapevine chips to repurpose this waste byproduct and assess its potential. We assessed the levels of trans-resveratrol, trans-ε-viniferin, trans-piceatannol, and the main resveratrol trimer. Our findings indicated a significant decrease in polyphenol content as the roasting temperature increased, from 16.85-21.12 mg GAE/g for grapevine chips roasted at 120 °C to 3.10-7.77 mg GAE/g for those roasted at 240 °C. This study also highlights notable genotypic differences in polyphenolic content. Among the red grape cultivars analyzed, Sorbara exhibited the highest levels (7.77-21.12 mg/GAEg), whereas the white grape cultivar Spergola showed the lowest polyphenolic content (3.10-16.85 mg/GAEg). These findings not only contribute to the scientific understanding of polyphenol stability but also hold practical implications for the enhancement of aged beverages, as well as advancing sustainable practices in the viticulture industries.

Effect of trans-resveratrol on glutamate clearance and visual behaviour in rats with glutamate induced retinal injury.

Glutamate-induced excitotoxic injury is widely described as a prominent pathophysiological mechanism in several neurodegenerative diseases including glaucoma. Glaucoma, the leading cause of irreversible blindness, is characterized by loss of retinal ganglion cells (RGC). Currently, the treatment focuses on lowering intraocular pressure (IOP) and no neuroprotective therapies are available. Since excessive glutamate-mediated neurotransmission underlies glaucomatous RGC apoptosis, enhancing synaptic glutamate clearance by glutamate transporters in glial cells is expected to protect against excitotoxic injury. Trans-resveratrol is known for its neuroprotective effects; however, its effects on the expression of glutamate transporters and glutamate clearance in retina remain unclear. Hence, in the current study, we investigated the protective effects of trans-resveratrol against glutamate-induced retinal injury in rats. Rats were intravitreally injected with glutamate alone or glutamate with trans-resveratrol as pre- and post-treatment. Animals were subjected to Open Field Test (OFT) on day six and a two-chamber mirror test on day seven post-injection. Subsequently, rats were sacrificed and retinal expression of excitatory amino acid transporter (EAAT)1 and EAAT2 gene and protein was determined using PCR and ELISA, respectively. Retinal glutamate concentration was measured using ELISA and retinal morphology was studied on H&E-stained retinal sections. It was observed that pre-treatment with trans-resveratrol causes gene expression for EAAT1 and EAAT2 to increase by 2.51 and 1.93 folds compared to glutamate-treated group (p < 0.001 and p < 0.01, respectively); while the same in trans-resveratrol post-treatment group showed a 1.58- and 1.44 folds upregulation (p < 0.05).The retinal EAAT1 and EAAT2 protein expression was significantly greater in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.05) but not in post-treatment group. Retinal glutamate concentration was1.64 folds greater in glutamate-treated group than the vehicle-treated group (p < 0.01) but the same was 1.27-fold lower in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.01). Corresponding to these findings, we observed preservation of retinal morphology and visual behaviour in trans-resveratrol pre-treatment group compared to glutamate-treated group. We did not observe similar effects of trans-resveratrol when it was given as post-treatment after glutamate administration. In conclusion, current study showed that pre-treatment with trans-resveratrol protects against glutamate induced changes in retinal morphology and visual behaviour by increasing the expression of EAAT1 and EAAT2 and increasing glutamate clearance in rat retinas. The results of this study may be relevant to disease conditions involving excitotoxic neuronal injury.

Characterization of the metabolites of trans-resveratrol-3-O-glucoside in monkeys and dogs.

In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MSn) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans-resveratrol-4'-O-glucuronide (M2'), trans-resveratrol-3-O-glucoside-4'-O-glucuronide (M3), trans-resveratrol-3-O-glucoside-5-O-glucuronide (M3'), trans-resveratrol-3-sulfate (M4) and trans-resveratrol-4'-sulfate (M4'). Additionally, the metabolic pathways of TRG in monkeys and dogs were proposed. There were also species differences of metabolism of TRG between monkeys and dogs.

Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells.

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.

Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin.

Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (endo coumarin-resveratrol-inspired hybrid) and trans-6-styrylcoumarin (exo coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with trans-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than trans-resveratrol.

Development of self-microemulsifying lipid-based formulations of trans-resveratrol by systematically constructing lipid-surfactant-water phase diagrams using long-chain lipids.

The aim of this work was to develop self-microemulsifying lipid-based formulations of trans-resveratrol in cod liver oil, a long chain lipid, to increase its solubility, dissolution rate and oral bioavailability. Ternary phase diagrams of cod liver oil with surfactant and water as well as pseudo-ternary phase diagrams of the same by mixing cod liver oil (triglyceride) with glycerol monooleate (monoglyeride) were constructed to identify regions where microemulsions were formed. Kolliphor RH 40, Tween 80 and their 1:1-mixtures were evaluated as surfactants. No organic cosolvents were added. It was observed that cod liver oil alone did not form microemulsion with any of the surfactants used, and a 1:1 mixture of cod liver oil and glycerol monooleate was necessary to enable the formation of microemulsion. Among the surfactants, Kolliphor RH 40 provided the maximum microemulsification effect. Several formulations containing 6:4, 1:1, and 4:6 w/w ratios of lipid to surfactant using the 1:1 mixture of cod liver oil and glycerol monooleate as lipid components and Kolliphor RH 40 or its mixture with Tween 80 as surfactants were identified, and trans-resveratrol solubility in these formulations were determined. Drug concentrations used in the formulations were 80% of saturation solubility, and no organic cosolvents were used in any formulations to increase drug solubility or enable emulsification. In vitro dispersion testing in 250 mL of 0.01 N HCl (pH 2) according to the USP method 2 at 50 RPM showed that the formulations rapidly dispersed in aqueous media forming microemulsions and there was no drug precipitation.

Addition of Trans-Resveratrol-Loaded Highly Concentrated Double Emulsion to Yoghurts: Effect on Physicochemical Properties.

Trans-resveratrol (RSV) needs to be encapsulated to maintain its beneficial properties on the human body. This is due to its extreme photosensitivity, short biological half-life, and easy oxidation. In this study, the use of double emulsions for RSV encapsulation and their further application on functional yoghurts was studied. Different types of yoghurts were prepared: with and without RSV and with two types of volumetric emulsion formulations (20/80 and 30/70). In order to study the influence of the addition of double emulsions to the physical properties of the prepared yoghurts, they were characterised fresh and after a month under storage at 4 °C, in terms of droplet size, morphology, stability, rheology, texturometry, colorimetry, and antioxidant capacity. Results obtained showed that the presence of emulsion in the yoghurts produced a generalised decrease in the predominant droplet size (from 48 µm to 15-25 µm) and an increase in the stability. Additionally, a predominantly elastic character was observed. The firmness values obtained were very similar for all the yoghurts analysed and did not suffer important modifications with time. A slight colour variation was observed with storage time in the control sample, whereas a more notable variation in the case of emulsion yoghurts was observed. An appreciable increase of the antioxidant capacity of the final functional yoghurt (100 g) was observed when it contained 5-8 mg of RSV. Encapsulated RSV added to yoghurts presented a larger protection against RSV oxidation compared with free RSV, presenting a larger antioxidant inhibition after one month of storage. Moreover, the antioxidant capacity of yoghurts with encapsulated RSV was not affected under storage, since slight reductions (3%) were registered after one month of storage at 4 °C.

Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures.

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy-entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2-318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsly-Roseman, Jouyban-Acree, and van't Hoff-Jouyban-Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10-2) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10-6) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization.

Sunscreens Containing Cyclodextrin Inclusion Complexes for Enhanced Efficiency: A Strategy for Skin Cancer Prevention.

Unprotected exposure of skin to solar ultraviolet radiation (UVR) may damage the DNA of skin cells and can lead to skin cancer. Sunscreens are topical formulations used to protect skin against UVR. The active ingredients of sunscreens are UV filters that absorb, scatter, and/or reflect UVR. Preventing the formation of free radicals and repairing DNA damages, natural antioxidants are also added to sunscreens as a second fold of protection against UVR. Antioxidants can help stabilise these formulations during the manufacturing process and upon application on skin. However, UV filters and antioxidants are both susceptible to degradation upon exposure to sunlight and oxygen. Additionally, due to their poor water solubility, natural antioxidants are challenging to formulate and exhibit limited penetration and bioavailability in the site of action (i.e., deeper skin layers). Cyclodextrins (CDs) are cyclic oligosaccharides that are capable of forming inclusion complexes with poorly soluble drugs, such as antioxidants. In this review, we discuss the use of CDs inclusion complexes to enhance the aqueous solubility of antioxidants and chemical UV filters and provide a protective shield against degradative factors. The role of CDs in providing a controlled drug release profile from sunscreens is also discussed. Finally, incorporating CDs inclusion complexes into sunscreens has the potential to increase their efficiency and hence improve their skin cancer prevention.

Comparative Analysis of the Antitumor Activity of Cis- and Trans-Resveratrol in Human Cancer Cells with Different p53 Status.

Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or- UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53(-/-)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.

Colorectal Adenocarcinoma Cell Culture in a Microfluidically Controlled Environment with a Static Molecular Gradient of Polyphenol.

To study the simultaneous effect of the molecular gradient of polyphenols (curcumin, trans-resveratrol, and wogonin) and biological factors released from tumor cells on apoptosis of adjacent cells, a novel microfluidic system was designed and manufactured. The small height/volume of microfluidic culture chambers and static conditions allowed for establishing the local microenvironment and maintaining undisturbed concentration profiles of naturally secreted from cells biochemical factors. In all trials, we observe that these conditions significantly affect cell viability by stimulating cell apoptosis at lower concentrations of polyphenols than in traditional multiwell cultures. The observed difference varied between 20.4-87.8% for curcumin, 11.0-37.5% for resveratrol, and 21.7-62.2% for wogonin. At low concentrations of polyphenols, the proapoptotic substances released from adjacent cells, like protein degradation products, significantly influence cell viability. The mean increase in cell mortality was 38.3% for microfluidic cultures. Our research has also confirmed that the gradient microsystem is useful in routine laboratory tests in the same way as a multiwell plate and may be treated as its replacement in the future. We elaborated the new repetitive procedures for cell culture and tests in static gradient conditions, which may become a gold standard of new drug investigations in the future.