Antioxidant activity and genotoxic effect on HeLa cells of phenolic compounds from infusions of Quercus resinosa leaves

Water infusions of mature and fresh Quercus resinosa leaves were evaluated for antioxidant activity and genotoxic effects on HeLa cells. Native Mexicans used to drink Q. resinosa leaves tea as a refreshing beverage. The air dried leaves were pulverised and boiled in water, then their phenolic content and condensed tannins were determined. The chromatographic profile of 15 phenolic components in Quercus leaves infusions was also determined by HPLC. In vitro analysis of antioxidant capacity of leaves infusion extracts were performed by the DPPH method and the deoxyribose assay. The genotoxicity of Q. resinosa leaves extracts was evaluated on HeLa cells as well as its underlying mechanism by the single-cell electrophoresis assay (comet assay). Results show that fresh leaves infusions increase the oxidative process and other damage to DNA in transformed human cells. Fresh leaves from Q. resinosa may serve as a potential source of phenolics with anticancer activity.     

Induction of apoptosis in U937 human leukaemia cells by the hexane fraction of an extract of immature Citrus grandis Osbeck fruits

The antiproliferative effect of an immature Citrus grandis Osbeck fruit extract was investigated using U937 human leukaemia cells. Maximum cytotoxicity was observed using the hexane fraction (HF) of the extract. Cell death was dose-dependent (IC₅₀ = ca. 60 μg/ml) and was characterised by chromatin condensation, apoptotic body formation, and DNA fragmentation. The induction of apoptosis was confirmed by caspase-3 activity assays and by immunoblotting using antibodies against Bcl-2, Bax, poly(ADP-ribose) polymerase (PARP), caspase-9, and caspase-3. The molecular mechanism underlying HF-induced apoptosis in U937 cells may involve a mitochondria-mediated signalling pathway, as demonstrated by an increase in the Bax/Bcl-2 expression ratio. Analyses of the HF by gas chromatography (GC) and GC-mass spectrometry (MS) tentatively identified 19 compounds, including γ-sitosterol (17.5%), 7-methoxy-8-(2-oxo-3-methylbutyl) coumarin (6.8%), stigmasterol (3.8%), and campesterol (3.4%). Together, our results provide the first evidence that the HF of an immature C. grandis Osbeck fruit extract induces apoptosis in U937 cells.     

Anticancer effect of lipids partially purified from Pacific oyster, Crassostrea gigas on PC3 cells

The objective of this study was to determine the anticancer effects of the Pacific oyster (Crassostrea gigas) in vitro. For this study, the lipid extracts of C. gigas were prepared using several organic solvents: methanol, chloroform, hexane, methanol:chloroform=1:1, chloroform: hexane=1:1. The anticancer activity of the extracts was evaluated using cell cycle and apoptosis assays analyzed by a flow cytometry. Of all the extracts, the hexane extracts exhibited the highest anticancer activity compared to the other extracts. The hexane extracts were further separated and purified using thin layer chromatography. The final isolated lipid compounds were identified their components as palmitic acid, margaric acid, and stearic acid. These results indicate that this combination of lipids effectively inhibit in vitro human prostate tumor growth by inducing apoptosis of cancer cells.     

Free radical scavenging activity and comparative proteomic analysis of antioxidative protein against H2O2-induced oxidative stress in neuronal cells

Artemisia annua was enzymatically hydrolyzed by five proteases and seven carbohydrases. All enzymatic extracts scavenged DPPH, hydroxyl and alkyl radicals. Especially, the Protamex among the various proteases and Maltogenase among the various carbohydrases extracts exhibited the highest scavenging activity on hydroxyl radical. The extracts of A. annua clearly reduced neuronal cell death from H₂O₂-induced damage. In addition, a proteomic analysis, two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionisation-time of flight/time of flight (MALDI-TOF/TOF) was used to identify the proteins of the neuronal cells whose expressions were or were not altered by the treatment of the Maltogenase extracts which showed the highest hydroxyl radical scavenging activity among all enzymatic extracts for 24 h. The protein characterisation revealed that translation elongation factor Tu (EF-Tu), Immunoglobulin E (IgE) and voltage-dependent anion channel 1 (VDAC-1) were involved in the cell survival effects against H₂O₂-induced apoptosis. These results suggest that EF-Tu, IgE and VDAC-1 have an important role in the reduction of neuronal apoptosis by oxidative stress, and the enzymatic extracts of A. annua shows potent antioxidative activities by regulating EF-Tu, IgE and VDAC-1.     

Induction of apoptosis by Myagropsis myagroides extracts is associated with a caspase dependent pathway and reactive oxygen species generation in human cancer cells

The purpose of this study was to elucidate the mechanisms underlying apoptosis induced by an ethanol extracts from Myagropsis myagroides (ME) in HeLa, U937, and PC-3 cells. ME treatment for 24 h significantly inhibited cell viability in a dose-dependent manner, and induced apoptosis. Moreover, ME treatment triggered the cleavage of caspase-8, ?9, ?3, and poly(ADP-ribose) polymerase (PARP). A general caspase inhibitor (z-VAD-fmk) inhibited ME-induced activation of caspase-3, PARP cleavage, and cell death. ME treatment also triggered the release of cytochrome c from the mitochondria to the cytosol and stimulated the cleavage of Bid, up-regulation of Bax, and down-regulation of Bcl-2. Furthermore, ME treatment caused reactive oxygen species (ROS) generation. An antioxidant N-acetylcysteine (NAC) blocked MEinduced activation of caspase-3, PARP cleavage, and cell death. Overall, these results suggest that ME-induced apoptosis is mediated by a caspase dependent pathway and ROS generation in HeLa, U937, and PC-3 cells.     

SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway

Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.     

Protective effect of Cordyceps militaris against high glucose-induced oxidative stress in human umbilical vein endothelial cells

The protective effect of Cordyceps militaris against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs), as compared with Cordyceps sinensis, was examined. The cytotoxicity of HUVECs induced by 40 mM glucose was ameliorated by water extracts of C. militaris (CME) and water extracts of C. sinensis (CSE). CME and CSE inhibited the increase in ROS and NO in HUVECs induced by 40 mM high glucose. Moreover, CME increased the Bcl-2/Bax ratio, modulated the mitochondrial membrane potential and reduced the caspase-3 activity in high glucose-induced HUVECs. In addition, cordycepin, a component of CME and CSE, displayed protective effects against oxidative stress, which was partly responsible for the cytoprotective effects of CME and CSE against high glucose-induced oxidative stress in HUVECs. Overall, the obtained results show C. militaris helps preventing diabetic endothelial dysfunction and related complications.     

Immunomodulatory and anticancer activities of phenolics from emblica fruit (Phyllanthus emblica L.)

There is a paucity of studies on the immunomodulatory properties of fruit extracts of emblica with the emphasis on lymphocytes. Therefore, the aim of the study was to evaluate the immunomodulatory properties and anticancer potential of six phenolic compounds from emblica fruit by in vitro proliferation assay. Effects of these compounds on splenocyte proliferation and the cytotoxicity to both human breast cancer cell (MCF-7) and human embryonic lung fibroblast cell (HELF) were determined by the MTT method. Significantly stimulatory effects (P < 0.05) were found for geraniin and isocorilagin. The concentration of geraniin, quercetin 3-β-d-glucopyranoside, kaempferol 3-β-d-glucopyranoside, isocorilagin, quercetin, kaempferol and rutin to obtain 50% of stimulatory effect was 56, 123, 242, 42, 73, 93 and 92 μg/ml, respectively. The assay of anticancer activities suggested that geraniin and isocorilagin exhibited higher cytotoxicities than other compounds against MCF-7 with IC₅₀ of 13.2 and 80.9 μg/ml, respectively. Isocorilagin exhibited a strong cytotoxicity to HELF cell with IC₅₀ of 51.4 μg/ml. Geraniin, quercetin, kaempferol and their glycosides had weak cytotoxicity against HELF cells. Paclitaxel showed a strong cytotoxicity to MCF-7 and HELF with IC₅₀ of 6.8 and 14.5 μg/ml, respectively. These findings are in line with the reported potent antioxidant activity. These results suggested that the antitumour activity of these compounds might be achieved by immunomodulatory properties which could partially be attributed to their antioxidant activity.     

Chemical composition, cytotoxicity effect and antimicrobial activity of Ceratonia siliqua essential oil with preservative effects against Listeria inoculated in minced beef meat

The present study describes the phytochemical profile and the protective effects of Ceratonia siliqua pods essential oil (CsEO), a food and medicinal plant widely distributed in Tunisia. Twenty five different components were identified in the CsEO. Among them, the major detected components were: Nonadecane, Heneicosane , Naphthalene, 1,2-Benzenedicarboxylic acid dibutylester, Heptadecane, Hexadecanoic acid, Octadecanoic acid, 1,2-Benzenedicarboxylic acid, Phenyl ethyl tiglate, Eicosene, Farnesol 3, Camphor, Nerolidol and n-Eicosane. The antimicrobial activity of CsEO was evaluated against a panel of 13 bacteria and 8 fungal strains using agar diffusion and broth microdilution methods. Results have shown that CsEO exhibited moderate to strong antimicrobial activity against the tested species. In addition, the inhibitory effect of this CsEO was evaluated in vivo against a foodborne pathogens Listeria monocytogenes, experimentally inoculated in minced beef meat (2 × 10² CFU/g of meat) amended with different concentrations of the CsEO and stored at 7 °C for 10 days. The antibacterial activity of CsEO in minced beef meat was clearly evident and its presence led to a strong inhibitory effect against the pathogens at 7 °C. On the other hand, the cytotoxic effects of the essential oil against two tumoral human cell lines HeLa and MCF-7 were examined by MTT assay. The CsEO showed an inhibition of both cell lines with significantly stronger activity against HeLa cells. The IC₅₀ values were 210 and 800 μg/ml for HeLa and MCF-7 cells, respectively. Overall, results presented here suggest that the EO of C. siliqua possesses antimicrobial and cytotoxic properties, and is therefore a potential source of active ingredients for food and pharmaceutical industry.     

Antioxidant activities and anticancer effects of red yeast rice grown in the medium containing garlic

The effects of culture time on antioxidant and anticancer activities of red yeast rice-garlic (RYRG) ethanol extracts were investigated. RYRG is a product of red yeast rice (Monascus pilosus) grown in medium containing garlic for 0, 2, 4, 6, and 8 weeks. The total phenolic and total flavonoid contents of RYRG extracts were increasing with the length of culture periods. The DPPH free radical scavenging activity of RYRG extracts also increased with culture time. The RYRG extracts prevented brain lipid peroxidation in culture time dependent manner. The RYRG extracts showed anti-proliferative effects against HepG2 human liver cancer cells, HT-29 human colon cancer cells, and B16F10 murine melanoma cells. The IC₅₀ value of 8-week fermented RYRG extract was the lowest among sample groups. Therefore, the results indicated that RYRG extracts exhibit culture time-dependent antioxidant and anti-cancer activities associated with the increase on phenolic and flavonoid contents. The RYRG extract is therefore a promising candidate as chemopreventive agents.     

Lycium barbarum polysaccharide inhibits the proliferation of HeLa cells by inducing apoptosis

BACKGROUND: Lycium barbarum polysaccharide (LBP), isolated with boiling water from the famous Chinese medicinal herb Lycium barbarum fruits, is one of the most important functional constituents in Lycium barbarum. In this study the effects of LBP on cell proliferation, cell cycle and apoptosis in human cervical carcinoma cells (HeLa cells) were investigated. RESULTS: LBP could inhibit the proliferation of HeLa cells by changing cell cycle distribution and inducing apoptosis. In addition, the loss of mitochondrial transmembrane potential (Δψ_m) was observed by flow cytometry and the increase of intracellular Ca²⁺ concentration was detected by laser scanning confocal microscope in apoptotic cells. At the same time, the nitric oxide content, nitric oxide synthase and inducible nitric oxide synthase activities were also increased. CONCLUSION: The inhibitory effect of LBP on the proliferation of HeLa cells was caused by inducing apoptosis through the mitochondrial pathway. The results showed that LBP can be developed as a potential chemotherapeutic agent candidate against human cervical cancer. Copyright © 2012 Society of Chemical Industry     

Molecular mechanism underlying anti-apoptotic and anti-inflammatory effects of Mamao (Antidesma thwaitesianum Müll. Arg.) polyphenolics in human breast epithelial cells

There has been increasing interest in finding natural antioxidants to prevent free radical damage and retard the progress of chronic inflammatory diseases. Our previous data demonstrated the strong antioxidant properties of polyphenolics in Mamao seed (MS) and Mamao marc (MM) extracts. In this study we further investigated the effect of MS and MM polyphenolics on hydrogen peroxide (H₂O₂)-induced apoptosis and tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, using human breast epithelial (MCF10A) cells. MS and MM extracts conferred dose-dependent protection against H₂O₂-induced apoptosis by inhibiting PARP/caspase-3 cleavage, inducing anti-apoptotic Bcl-2 expression, and down-regulating pro-apoptotic Bax. Moreover, MS and MM polyphenolics inhibited TPA-induced COX-2 and NF-κB activation by blocking the degradation of cytoplasmic IκBα, as well as subsequent nuclear translocation of p65 and attenuation of the activation of ERK, but not JNK and p38. These data establish the molecular mechanism for the anti-apoptotic and anti-inflammatory effects of MS and MM polyphenolics.     

Phenolic content, antioxidant, anti-inflammatory and anticancer activities of the edible halophyte Suaeda fruticosa Forssk

Suaeda fruticosa is an edible and medicinal halophyte known for its hypoglycaemic and hypolipidaemic activities. In this study, novel biological activities of the shoot extracts related to their phenolics were investigated. Results showed an appreciable total phenolic (31.8 mg GAE/g DW) in shoot extracts. The estimation of antioxidant capacities using oxygen radical absorbance capacity (ORAC method) and a cell based-assay (WS1) of four extracts (hexane, dichloromethane, methanol and water) showed that shoot methanol extract exhibit the highest antioxidant activities. The same extract displayed the utmost anti-inflammatory activity, inhibiting nitric oxide (NO) release, by 66.4% at 160 μg/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Besides, the dichloromethane extract showed the highest anticancer activity against human lung carcinoma (A-549) and colon adenocarcinoma cell lines (DLD-1, Caco-2 and HT-29) with specificity against DLD-1 (IC₅₀ = 10 ± 1 μg/ml). These findings demonstrate the remarkable potentiality of this edible halophyte as valuable source of antioxidants which exhibit original and interesting anti-inflammatory and anticancer capacities.     

Effects of Salvia officinalis and Thymus vulgaris on oxidant-induced DNA damage and antioxidant status in HepG2 cells

Salvia officinalis (SO) and Thymus vulgaris (TV) are medicinal plants well known for their curative powers. However, the molecular mechanisms responsible for these abilities of sage and thyme have not been fully understood yet. In this study we investigated the composition and the quantitative estimation of plant extracts, the protective effects of plant extracts against hydrogen peroxide- and 2,3-dimethoxy-1,4-naphthoquinone-induced DNA damage, and levels of enzymatic and non-enzymatic antioxidants (superoxide dismutase, glutathione peroxidase, glutathione) in human HepG2 cells. To measure antioxidative activity of plant extracts we used three assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The results showed that the oxidant-induced DNA lesions were significantly reduced in cells pre-treated with the plant extracts studied. The observed DNA-protective activity could be explained by both elevation of GPx activity in cells pre-treated with SO and TV and antioxidant activity of SO and TV.     

Anti‐inflammatory and anticancer activities of water‐soluble peptide extracts of buffalo and cow milk Cheddar cheeses

This article aimed to assess the anti‐inflammatory and anticancer potential of water‐soluble peptide (WSP) extracts from buffalo and cow milk Cheddar cheeses. Anti‐inflammatory activity was evaluated on the basis of nitric oxide (NO) production in lipopolysaccharide‐stimulated macrophage (RAW‐264.7) cells. A cell viability assay, cell cycle arrest and apoptosis were performed to explore anticancer activity in a colon cancer model (HT‐29). The WSP extracts of both Cheddar cheeses effectively inhibited NO production in activated macrophages. Maximum growth inhibition was observed in the HT‐29 cells at concentrations of 400 and 500 μg/mL. A significant increase in cell population at G₀/G₁ phase of the cell cycle was observed. Moreover, the WSP extracts also induced extensive apoptosis in colon cancer cells.     

Analysis of the isothiocyanates present in three Chinese Brassica vegetable seeds and their potential anticancer bioactivities

Epidemiological studies give evidence that high dietary intake of cruciferous vegetables has been associated with lower risk of cancer, this activity due to their content in glucosinolates (GL), which upon myrosinase hydrolysis release the corresponding isothiocyanates (ITCs). In this study, the isothiocyanates contents and the anticancer activity of ethyl acetate extracts from three kinds of Chinese Brassica vegetable seeds have been examined and analyzed. A correlation was found between the potency of anticancer activity and the amount of isothiocyanates in their extracts. Extracts followed by GC–MS analysis revealed that 3-BITC (3-butenyl isothiocyanate) was mainly found in Chinese kale contained 77.58 ± 7.28 mg/g (dry weight); AITC (allyl isothiocyanate), 3-BITC and iberverin were the predominant isothiocyanates in Oxheart cabbage contained 33.57 ± 3.94, 26.50 ± 1.92 and 22.77 ± 0.00 mg/g, respectively; 3-BITC and sulforaphane were found as the major isothiocyanates in broccoli contained 138.52 ± 3.42 and 49.77 ± 0.18 mg/g, respectively. The amount of total isothiocyanates in broccoli was twice higher than that in other two species. The anticancer activity of broccoli was the highest, and the IC₅₀ value of the extract inhibiting on the growth of A549, LAC, HELA and HepG₂ were 14.38 ± 0.35, 10.38 ± 0.34, 19.45 ± 1.72 and 26.75 ± 0.82 mg/g, respectively. The extracts of Chinese Brassica vegetable seeds have the potential in inducing cancer cells apoptosis by morphology observation. The results of this study got a new kind of Brassica vegetable seeds that could produce high content of isothiocyanates, which is important to preparation of anticancer food additives.     

Anthocyanin compositions and biological activities from the red petals of Korean edible rose (Rosa hybrida cv. Noblered)

The objectives of the present study were to investigate anthocyanin profiles and their biological properties, including antioxidant, anticancer, and antiallergic, from the red petals of Korean edible rose (Rosa hybrida cv. Noblered). The acidic methanol extract of this species showed potent biological activities at a concentration of 50 μg/mL. Its anthocyanins were characterised as cyanidin 3,5-di-O-glucoside and pelargonidin 3,5-di-O-glucoside using reversed-phase C₁₈ column chromatography, NMR spectroscopy, and HPLC-DAD-ESI/MS analysis. Cyanidin 3,5-di-O-glucoside was the predominant constituent (375 mg/100 g), representing about 85% of total content. Cyanidin 3,5-di-O-glucoside exhibited good scavenging activity against DPPH radical with IC₅₀ value of 55.2 μg/mL; pelargonidin 3,5-di-O-glucoside showed potent anticancer effects against LNCap (human prostate cell line), ACHN (human renal cell line) and MOLT-4F (human leukaemia cell line) cell cultures, with IC₅₀ values of 6.43, 18.3, and 6.78 μg/mL, respectively. Antiallergic activities were only moderate.     

AKT signalling and mitochondrial pathways are involved in mushroom polysaccharide-induced apoptosis and G1 or S phase arrest in human hepatoma cells

This study describes molecular mechanisms for inhibiting tumour cell proliferation using polysaccharides from medicinal mushrooms in human hepatoma cells. The results show that regarding cell cycle-related proteins, three types of polysaccharides significantly enhance the expression of p27^Kip in HepG2 and Bel-7404 cells, while suppressing the activity of cyclin D1/CDK4 and/or cyclin E/CDK2. Considering apoptosis-related factors, the polysaccharides suppressed AKT activity through the inhibition of AKT phosphorylation at Thr³⁰⁸ and/or Ser⁴⁷³. The growth of HepG2 and Bel-7404 cells was suppressed by the up-regulation of a subunit of PI3K and phospho-PTEN, which are modulators of AKT activity. The polysaccharides also activated the mitochondria-mediated apoptosis pathway by stimulating the activation of Bcl-2 family proteins to release cytochrome c and Smac and cleave caspase-9 and caspase-3 in HepG2 and Bel-7404 cells. These factors have a potent effect on cell cycle arrest in G₁ and/or S phase and induce apoptosis in HepG2 and Bel-7404 cells.     

Cladonia lichens and their major metabolites as possible natural antioxidant,antimicrobial and anticancer agents

The aim of this study is to investigate in vitro antioxidant, antimicrobial, and anticancer activities of the acetone extracts of the lichens Cladonia furcata, Cladonia pyxidata and Cladonia rangiferina and their atranorin and fumarprotocetraric acid constituents. Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power, and determination of total phenolic and flavonoid compounds. As a result of the study atranorin had largest free radical scavenging activity with IC₅₀ values 131.48 μg/mL. Moreover, the tested samples had effective reducing power and superoxide anion radical scavenging. Total content of phenol and flavonoid in extracts was determined as pyrocatechol equivalent, and as rutin equivalent, respectively. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was fumarprotocetraric acid with minimum inhibitory concentration values ranging from 0.031 to 0.125 mg/mL. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method. All samples were found to be strong anticancer activity toward both cell lines with IC₅₀ values ranging from 10.97 to 41.23 μg/mL.     

Oxidative stress prevention and anti-apoptosis activity of grape (Vitis vinifera L.) stems in human keratinocytes

To date, grape stems have been partially assessed on their content in phenolics and their radical scavenging activity, whilst the potential to modulate oxidative stress in biological models remains underexplored. In the present work, the effect of grape stems' phenolics on redox unbalance was evaluated in human keratinocytes (HaCaT cells). Grape stems' extracts were assessed on their phenolic composition by high performance liquid chromatography coupled with photodiode array detection and electrospray ionization-mass spectrometry (HPLC–PAD-ESi-MSn), besides on radical scavenging capacity (ABTS and DPPH). In addition, their protective effect against oxidative stress induced by H₂O₂ by the determination of the level of glutathione, reactive oxygen species, lipid peroxidation, and overall oxidative stress in HaCaT cells by flow cytometry was evaluated. This characterization allowed to identify five flavonols, one cinnamic acid, and one stilbene. A close correlation between the concentration of these phenolics and the capacity to scavenge free radicals and with the potential to modulate the redox balance in vitro was observed. From the analysis of correlation, the activity of malvidin-3-O-glucoside, malvidin-3-O-(6-O-caffeoyl)-glucoside, and malvidin-3-O-rutinoside with respect to the prevention of basal oxidative stress and the capacity of isorhamnetin-3-O-(6-O-feruloyl)-glucoside and kaempferol-3-O-rutinoside to prevent H₂O₂-induced redox unbalance were stated. Furthermore, grape stems' phenolics also showed an efficient capacity to modulate apoptosis in HaCaT cells, reducing the frequency of annexin V/PI double positive apoptotic cells by up to 99.5% relative to controls, which was further confirmed by the determination of the appearance of the occurrence of apoptotic bodies and the expression of activated (cleaved) caspase-3 by flow cytometry and western-blot, respectively. These results supported the potential of individual phenolics from grape stems to modulate oxidative stress, allowing to envisage dedicated combinations of single compounds for the development of efficient formulations efficient against oxidative stress.