Antioxidant Activity Of Resveratrol Research Articles

Nanoparticles prepared with biotin-esterified debranched starch as an oral carrier to improve the stability and antioxidant activity of resveratrol

In this study, biotin esterified debranched starch (Bio-DBS) nanoparticles with different molecular weights were prepared to improve the stability and antioxidant activity of resveratrol. The molecular weights of branched starch (DBS3, DBS9 and DBSp) determined by high-performance size-exclusion chromatography (HPSEC) were 3306, 3696, and 4688, respectively. Biotin was covalently coupled to DBS through the esterification reaction as a new material to prepare nanoparticles. The morphology, particle size, and loading capacity of Bio-DBS nanoparticles were all related to the molecular weights of DBS. The 1H NMR results indicated that there was a hydrogen bonding interaction between Bio-DBS and resveratrol, which contributed to the photochemical and antioxidant activity of resveratrol in the nanoparticles. The highest encapsulation efficiency (78.9 %) and loading capacity (15.78 %) of resveratrol were observed in Bio-DBS3 nanoparticles. Additionally, the cell viability was over 80 % when the concentration of Bio-DBS3 reached to 200 μg/mL. The Bio-DBS nanoparticles significantly improved the thermal stability, photostability, and antioxidant properties of resveratrol. Therefore, the Bio-DBS nanoparticles prepared in this study can be used as a promising carrier to improve the stability and antioxidant activity of resveratrol and may have potential applications in oral delivery.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

Study of the Antioxidant Capacity and Oxidation Products of Resveratrol in Soybean Oil.

Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol that is widely utilized in functional food due to its antioxidant, anti-inflammatory, anti-cancer and anti-aging properties. In the present study, the antioxidant capacity and oxidation products of resveratrol in soybean oil were investigated. The antioxidant activity of resveratrol was evaluated by employing various in vitro antioxidant assays such as DPPH scavenging activities, ferric reducing abilities (FRAP) and oxygen radical absorbance capacity (ORAC). Furthermore, monitoring the peroxide value and the acid value of soybean oil with the addition of 200-1000 μg/g of resveratrol at 60 and 180 °C. It was found that when the concentration of resveratrol in soybean oil was 600 µg/g, the antioxidant capacity was most effective. Resveratrol and its thermal degradation products were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). There were seven nonvolatile oxidation products with mass-to-charge ratios of 138.03, 171.04, 185.10, 157.03, 436.13, 244.07 and 306.09 kg/C and two volatile oxidation products with mass-to-charge ratios of 100.05 and 158.13 kg/C were identified. The research findings may provide essential information for the development of resveratrol as functional oils in future.

Enhanced solubility, thermal stability and antioxidant activity of resveratrol by complexation with ovalbumin amyloid-like fibrils: Effect of pH

Resveratrol (RES) has attracted much attention because of its many potential health benefits. However, its poor aqueous solubility and chemical instability hinder its application. In this study, ovalbumin (OVA) fibrils (OVAF) were used as nanocarriers to improve the aqueous solubility, thermal stability and antioxidant activity of hydrophobic RES, and the effects of pH were also investigated. The results showed that after complexation with OVAF at pH 2.0, the aqueous solubility of RES was 12.3 times higher than that of free RES. Transmission electron microscope images revealed that after incorporating with RES, the OVAF assembled into entangled aggregates due to the interaction. Intrinsic fluorescence spectra, Fourier transform infrared spectra and zeta potential measurements showed that the hydrophobic interactions, hydrogen bonds and electrostatic interactions were mainly contributed to the formation of OVAF/RES complex. Moreover, X-ray diffraction results proved that RES was encapsulated in fibrils with an amorphous form. It was noteworthy that OVAF at pH 2.0 had the highest binding constant with RES, and thus it exhibited the best protective effect on thermal degradation of RES. In addition, the antioxidant capacity of RES was drastically improved through the complexation with OVAF. Hence, these results suggested that OVA amyloid-like fibrils may be a suitable nanocarriers for hydrophobic nutrients.

The effect of the antioxidant system resveratrol - iron sulfonitrosyl complex sodium-μ2-dithiosulphate-tetrarntrosyl diferrate tetrahydrate on the mitochondria of pea germ epicotyls in vitro

The interaction of antioxidants - plant polyphenol resveratrol and nitric oxide donor, iron-sulfo-nitrosyl complex with thiosulfate Na2[Fe2(S2O3)2(N0)4]24H2O (TNIC-thio), and their combined action on mitochondria of pea germ epicotyls was studied in vitro. The antioxidant activity of resveratrol (10-6 M), partially compensated the toxic effect of TNIC-thio at high concentration, that is most likely associated with the exhibition of the prooxidant properties of high concentrations of the nitric oxide donor. The effect of resveratrol at concentrations 10-6 M and 10-8 M on the membranes of mitochondria isolated from the pea germ epicotyls treated with 10-8 M TNIC-thio led to coordinations failure in the system of regulation of lipid peroxidation of membranes, that caused antioxidant stress. The action of resveratrol at the dose of 240-5 M had a dual character and practically did not effect on the structural state of mitochondrial membranes.

Studies on the Anticancer and Antioxidant Activities of Resveratrol and Long-Chain Fatty Acid Esters.

Resveratrol (RES) is gaining recognition as a natural bioactive compound. To expand the possible applications of RES with its enhanced bioactivity as well as to increase the health benefits of long-chain fatty acids, a lipophilization process of RES was performed using three fatty acids: palmitic acid (PA), oleic acid (OA), and conjugated linoleic acid (CLA). The obtained mono-, di-, and tri-esters of RES were evaluated for their anticancer and antioxidant properties against lung carcinoma (A549), colorectal adenocarcinoma (HT29), and pancreatic ductal adenocarcinoma (BxPC3) cell lines. Human fibroblast (BJ) cells were used as a control. Several parameters were investigated: cell viability and apoptosis, including the expression of major pro- and anti-apoptotic markers, as well as the expression of superoxide dismutase, a key enzyme of the body's antioxidant barrier. Three of the obtained esters: mono-RES-OA, mono-RES-CLA, and tri-RES-PA, which significantly reduced the tumor cell viability up to 23%, at concentrations 25, 10, 50 μg/mL, respectively, turned out to be particularly interesting. The above-mentioned resveratrol derivatives similarly increased the tumor cells' apoptosis by modifying their caspase activity of pro-apoptotic pathways (p21, p53, and Bax). Moreover, among the mentioned esters, mono-RES-OA induced apoptosis of the analyzed cell lines most strongly, reducing the number of viable cells up to 48% for HT29 cells versus 36% for pure RES. Furthermore, the selected esters exhibited antioxidant properties towards the normal BJ cell line by regulating the expression of major pro-antioxidant genes (superoxide dismutases-SOD1 and SOD2) without the effect on their expression in the tumor, and therefore reducing the defense of cancer cells against increased oxidative stress induced by high ROS accumulation. The obtained results indicate that the esters of RES and long-chain fatty acids allow enhancement of their biological activity. The RES derivatives have the potential for being applied in cancer prevention and treatment, as well as for oxidative stress suppression.

Oxidized Chitin Nanocrystals Greatly Strengthen the Stability of Resveratrol-Loaded Gliadin Nanoparticles.

Resveratrol (RES) is a natural polyphenol with a variety of health beneficial properties, but its application is greatly limited due to low aqueous solubility and poor bioavailability. This study aims to address these issues via gliadin nanoparticles stabilized with oxidized chitin nanocrystals (O-ChNCs) as a delivery system for RES. RES-loaded gliadin nanoparticles (GRNPs) were fabricated by an antisolvent method, and their formation mechanism was elucidated using zeta-potential, FTIR, XRD, and TEM. Furthermore, the effect of O-ChNCs on the colloidal stability and bioactiveness of GRNPs was discussed. The results demonstrate that O-ChNCs are adsorbed onto the surface of GRNPs through hydrogen bonding and electrostatic interactions, leading to the enhanced absolute potential and the improved hydrophobicity of the particles, which in turn facilitates the stability of the GRNPs. Furthermore, the changes in the release profile and antioxidant activity of RES in the simulated gastric and intestinal tracts indicate that the adsorption of O-ChNCs not only delays the release of RES but also has a protective effect on the antioxidant capacity of RES. This study provides significant implications for developing stable gliadin nanoparticles as delivery vehicles for bioactive substances.

Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors.

Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an ethoxy-substituted compound (7), and two ethoxy-substitute,0d dimers (8 and 9). Compounds 4, 7, 8, and 9 are reported here for the first time. All compounds without ethoxy substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies, compounds 2 and 4 were identified as potent competitive inhibitors of the enzyme, while compound 3 and the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound.

Encapsulation of trans-resveratrol in poly(ε-caprolactone) by GAS antisolvent

In this study, poly(ε-caprolactone) particles containing resveratrol were developed employing the GAS antisolvent technique. A central composite design 22 evaluated the influence of polymer, resveratrol mass ratio (2:1, 1:1, 1:2), and pressure (100, 120, 140 bar) on encapsulation percentage, and efficiency. The values obtained for encapsulation efficiency and percentage of encapsulation at the best conditions attained were 99.34% and 65.31%. In addition, the statistical analysis showed that only the mass ratio had significantly affected the percentage of encapsulation, but neither variable significantly affected efficiency. Microparticles produced demonstrably heterogeneous characteristics and irregular morphology. However, this process did not change either the compound chemical structures or the resveratrol antioxidant activity. Microparticles maintained constant release for 48 h, and in thermal oxidative analysis, the difference between samples and control was 2.57 times smaller than the difference between pure resveratrol and the control sample.

Ecological formulation for improving resveratrol stability and release in aqueous environment

Resveratrol (RES) is a naturally occurring product with numerous biological activities. Despite its potential benefits, its use is limited due to its low aqueous stability and solubility in its native form. The porous sol–gel silica materials which are able to entrap different organic molecules represent new studied release carriers. The aim of this work was to generate a solid matrix to encapsulate RES ensuring protection, increased solubility and release in solutions. A non-toxic ingredient, namely β-cyclodextrin (β-CD), able to form inclusion complexes (ICs) with RES has been used. Ecological formulations have been processed by entrapping the RES containing ICs in silica matrices obtained from a silica colloidal sol by the aqueous route of the sol–gel method. Characterization methods (DSC, FTIR, UV–Vis, fluorescence studies, SEM) have evidenced the presence of RES–β-CD inclusion complex in the silica powder, RES stability in the matrix and its release in aqueous and organic solutions, and the morphology of the carrier. An evaluation of the antioxidant activity of RES in the present formulation was performed by the chemiluminescence assay and RES release profile in aqueous solutions was obtained by HPLC–MS. The resulted materials can find applications in different domains.

Liposomes as carriers of resveratrol and vitamin E: Evaluating ameliorative antioxidant effect using chemical and cellular test systems.

Resveratrol (RES) in combination with antioxidant vitamins is reported to be more effective in protecting the cells from oxidative stress rather than any of these antioxidants alone. In continuation to our previous work using resveratrol and vitamin C, our main aim was to evaluate the antioxidant restorative effect using chemical and cellular test systems on resveratrol co-encapsulated vitamin E (VE) within liposomes. Z-average size was less than 135nm, polydispersity index<0.3; zeta potential>than±30mV and encapsulation efficiency of RES and VE>90% and 79% respectively. Chemiluminescence measurement indicated that the antioxidative activity of RES could be increased when VE was additionally loaded into liposomes. Inhibition of AAPH induced luminol enhanced chemiluminescence displayed 90% improvement (P<0.001) in comparison to control; on the other hand 70% luminescence inhibition of ROS production in isolated blood leukocytes (P<0.001) was observed. Intracellular oxygen-derived radicals measured by flow cytometry using 2'-7'-dichlorodihydrofluorescein diacetate demonstrated about 1.7 fold (P<0.05) and 1.5 fold (P<0.001) enhancement of radical scavenging activity in buffy coats under basal conditions and human umbilical vein endothelial cells after stimulation by H2O2 respectively. The cellular systems evidenced the ability of liposome loaded antioxidants to scavenge ROS in the extra and intracellular space, confirming enhanced antioxidative effectivity of RES in the presence of VE, which did not occur in combination with vitamin C. Hence it might be possible to improve the antioxidative effectivity of RES by other/additional antioxidants.

α-Lactalbumin and chitosan core-shell nanoparticles: resveratrol loading, protection, and antioxidant activity.

Resveratrol (RES)-loaded protein-polysaccharide nanoparticles were fabricated through simple electrostatic interactions with oppositely charged α-lactalbumin (ALA) and chitosan (CHI) with a mass ratio of 5 : 1 without the addition of NaCl at pH 6.5. The Z-average diameter and zeta-potential values of RES-ALA-CHI nanoparticles were 211.0 nm and 13.23 mV, respectively. Both TEM and AFM graphs confirmed that RES-ALA-CHI nanoparticles had a spherical shape, and were dispersed homogeneously at the nanoscale. The encapsulation efficiency (EE) and loading amount (LA) of RES in RES-ALA-CHI nanoparticles were 58.86% and 196.2 μg mg-1, respectively, in the presence of 400 μg mL-1 RES. XRD results confirmed that RES was in amorphous form in ALA-CHI nanoparticles. The interaction between RES and ALA-CHI nanoparticles was mainly driven by hydrophobic interaction and hydrogen bonding. Compared to RES (free), the UV light and heat stability, in vitro bioaccessibility, and antioxidant activity of RES in RES-ALA-CHI nanoparticles were pronouncedly enhanced. The information provided in this study should be of interest to the food industry to fabricate robust nanoscale delivery systems with ALA-CHI nanoparticles for RES and other hydrophobic bioactive compounds.

Influence of Resveratrol on the Immune Response.

Resveratrol is the most well-known polyphenolic stilbenoid, present in grapes, mulberries, peanuts, rhubarb, and in several other plants. Resveratrol can play a beneficial role in the prevention and in the progression of chronic diseases related to inflammation such as diabetes, obesity, cardiovascular diseases, neurodegeneration, and cancers among other conditions. Moreover, resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. At the molecular level, it targets sirtuin, adenosine monophosphate kinase, nuclear factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis. Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes’ expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties. The effects of this biologically active compound on the immune system are associated with widespread health benefits for different autoimmune and chronic inflammatory diseases. This review offers a systematic understanding of how resveratrol targets multiple inflammatory components and exerts immune-regulatory effects on immune cells.

Антиоксидантная активность и клиническая эффективность биологически активной добавки Нефрадоз в лечении рецидивирующего кальций-оксалатного уролитиаза

to evaluate antioxidant properties of dietary supplements Nefradoz, as well as its role in the prevention of calcium oxalate stones. Our study consisted of two parts, clinical and experimental. In the clinical trial a total of 80 patients with recurrent calcium oxalate urolithiasis of various localization were included. All patients were divided into 2 groups. In treatment group (n=45) patients received Nefradoz 1 capsule 2 times a day. In control group (n=35) no treatment was prescribed. In all patients a biomarkers level (bikunin, osteopontin, nephrocalcin) in urine was determined by ELISA. In addition, Litos-test was performed. Follow-up duration was 6 months. In the experimental part of the study, the antioxidant properties of Nefradoz were evaluated using chemiluminescence method. The antioxidant activity of resveratrol, which is contained in 300 mg Nefradoz (1 capsule), was 23.66+/-1.18, which corresponds to the moderate activity. After 6 months of therapy a level of bikunin and osteopontin did not significantly changed, which indicates a minimal risk of stone recurrence. According to the Litos-test, the activity of stone formation in Nefradoz group significantly decreased to minimal values in 42 out 45 patients (p<0.05). In the control group an excretion of biomarkers was minimal, which significantly increased the risk of stone formation. Dietary supplement NefraDoz can be used for prevention of calcium oxalate urolithiasis in case of increased stone formation according to the Litos-test. The antispasmodic, uroseptic and diuretic effects allow to maintain the effective level of biomarkers which is required for a recurrence-free course of urolithiasis compared to the control. The antioxidant activity, primarily determined by the resveratrol, can sufficiently compensate for oxidative stress and prevent the development of calcium oxalate stone. Further studies are needed to confirm our results.

Improvement in dispersibility, stability and antioxidant activity of resveratrol using a colloidal nanodispersion of BSA-resveratrol

Resveratrol has low aqueous stability and solubility in its native form that restricts its use in fortifying food products. The influence of bovine serum albumin (BSA)-trans-resveratrol complex on the solubility, photochemical stability and antioxidant activity of trans-resveratrol was studied using UV and fluorescence spectroscopy techniques, oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays. The results showed that resveratrol was solubilized using BSA at a molar ratio of 2.3:1 of resveratrol:BSA. FTIR and fluorescence spectroscopy techniques verified the formation of the BSA-resveratrol complex. The results of UV spectroscopy showed that the formation of the complex significantly protected resveratrol from UV-induced isomerization. The FRAP values for resveratrol-BSA were decreased compared to free resveratrol (57% in 30:30 resveratrol-BSA, 39% in 90–90 resveratrol-BSA and 25% in 300:300 resveratrol-BSA μM concentration). ORAC assays showed an almost 3 folds decrease in antioxidant activity of resveratrol after 3 days; however, ORAC values for BSA-resveratrol complexes were not significantly changed. BSA was successfully used to improve resveratrol solubility and stability in aqueous medium. This approach may increase the daily intake of unchanged resveratrol by consumers of fortified beverages using this system.

Enhanced pH and thermal stability, solubility and antioxidant activity of resveratrol by nanocomplexation with α-lactalbumin.

The health-promoting benefits of resveratrol (RES) have attracted significant attention. Poor water solubility and chemical stability, however, hindered its application. In this study, α-lactalbumin (ALA)-RES nanoparticles were prepared by a simple nanocomplexation protocol. The particle sizes of ALA and the ALA-RES complex were 87.8, and 95.3 nm, respectively. AFM confirmed that both nanoparticles were spherical. XRD results confirmed that RES in ALA nanoparticles was amorphous. Fluorescence spectroscopy and FTIR showed that the ALA-RES nanocomplex was formed mainly by hydrophobic interactions. The water solubility increased by 32 times, compared to that of free RES. ALA nanocomplexation also appreciably improved the chemical stability of RES under all storage conditions, especially at pH 8.0 and high temperature. The ALA-RES nanocomplex showed significantly higher in vitro antioxidant activity than free RES. The results showed that the simple ALA-RES nanocomplex has the potential to be used as an effective antioxidant. The information obtained may enable the expanded application of ALA as an effective nanoscale carrier for delivering RES or other lipophilic nutraceuticals in the functional food, biomedical, and pharmaceutical products.

Methodologies in the re-evaluation of nitrates and nitrites by the European Food Safety Authority (EFSA)

Folic acid is a synthetic form of the B-group vitamin known as folate and essential for a variety of physiological processes. However, it decomposes under UV irradiation, causing indirect oxidation and structural change of protein. In this study, the protective effect of resveratrol against the photodecomposition of folic acid and its caused protein structural change was investigated by using fluorescence and absorbance spectroscopy, high performance liquid chromatography and ABTS assay. It was found that resveratrol could inhibit the folic acid decomposition and control the decomposition process, depending on the polyphenol concentration and addition time. Transformation of resveratrol was accelerated by photodecomposition of folic acid. Antioxidant activity of resveratrol was important for the protective effect. Moreover, resveratrol could also inhibit the unfolding of beta-lactoglobulin caused by the folic acid decomposition by using circular dichroism.

Protection of resveratrol against the photodecomposition of folic acid and photodecomposition-induced structural change of beta-lactoglobulin

Folic acid is a synthetic form of the B-group vitamin known as folate and essential for a variety of physiological processes. However, it decomposes under UV irradiation, causing indirect oxidation and structural change of protein. In this study, the protective effect of resveratrol against the photodecomposition of folic acid and its caused protein structural change was investigated by using fluorescence and absorbance spectroscopy, high performance liquid chromatography and ABTS assay. It was found that resveratrol could inhibit the folic acid decomposition and control the decomposition process, depending on the polyphenol concentration and addition time. Transformation of resveratrol was accelerated by photodecomposition of folic acid. Antioxidant activity of resveratrol was important for the protective effect. Moreover, resveratrol could also inhibit the unfolding of beta-lactoglobulin caused by the folic acid decomposition by using circular dichroism.

In vitro antioxidant activities of resveratrol, cinnamaldehyde and their synergistic effect against cyadox-induced cytotoxicity in rabbit erythrocytes

This study was conducted to explore the potential benefits of using cinnamaldehyde (CIN), resveratrol (RES) separately or in combination on cyadox (CYA)-induced alterations in isolated rabbit erythrocytes. Erythrocytes suspensions were partitioned into 7 groups (5 replicates/group), 1st kept as control treated with phosphate buffered saline (PBS) with dimethyl sulphoxide (DMSO); 2nd group was subjected to CYA (40 μg/ml), 3rd group was incubated with CIN (40 μM), 4th group was subjected to RES (40 μM), 5th group was co-exposed to CYA (40 μg/ml) and CIN (40 μM), 6th group was co exposed to CYA (40 μg/ml) and RES (40 μM), and 7th group was exposed to CYA in combination with both CIN and RES at the same indicated concentrations. The reaction mixtures of different groups were incubated at 37 °C for 3 h with gentle shaking every 15 minutes. Our results revealed that exposure to CYA caused a significant decrease (linear and quadratic) in superoxide dismutase (SOD) and catalase (CAT) activities and the contents of reduced glutathione (GSH) and glutathione transferase (GST). Incubation of erythrocytes with CYA increased GSSG content, GSSG/GSH ratio, malonaldehyde (MDA) and protein carbonyl (PrC) concentrations while it decreased the total protein (TP). CYA also lead to hemolysis and energy depletion of erythrocytes beside activation of caspase cascades, suggesting the pro-oxidant effect CYA that could be implicated in eryptosis. CIN and RES were able to inverse these hazardous effects of CYA. However, CIN was more effective than RES, their combination showed a positive synergistic effect in protecting the cells against oxidative injury caused by CYA.

Enhancing Topical Delivery of Resveratrol through a Nanosizing Approach.

Resveratrol is a naturally occurring polyphenol with strong antioxidant and free radical scavenging properties, recently proposed as a therapeutic agent for skin diseases. In this study, we investigated the possibility of improving the dermal bioavailability of the poorly water-soluble drug resveratrol by nanocrystal technology. To this purpose, nanosuspensions were prepared by the wet media milling technique, using Poloxamer 188 or Tween 80 as stabilizers, and characterized by means of both solid state and morphological and dimensional studies. All analytical data demonstrated that neither a modification of the drug crystalline pattern nor the isomerization of the trans double bond were observed after the wet media milling particle size reduction process, which produced rounded and smooth nanocrystals with a mean diameter ranging between 0.2-0.3 µm. Resveratrol skin delivery from nanosuspension formulations was evaluated by the pig ear skin model via tape stripping. Results of the experiments showed that after application of nanosuspension formulations, higher amounts of resveratrol could penetrate the skin at deeper levels compared to drug coarse suspensions. The antioxidant activity of resveratrol in nanocrystals was assessed by the DPPH assay, which demonstrated that the size reduction process as well as the formulation compositions did not modify the drug antioxidant activity.