Grape Seed Extract Treatment Research Articles

Phytochemical Profiling and Bioactive Potential of Grape Seed Extract in Enhancing Salinity Tolerance of Vicia faba.

Salinity stress poses a significant threat to crop productivity worldwide, necessitating effective mitigation strategies. This study investigated the phytochemical composition and potential of grape seed extract (GSE) to mitigate salinity stress effects on faba bean plants. GC-MS analysis revealed several bioactive components in GSE, predominantly fatty acids. GSE was rich in essential nutrients and possessed a high antioxidant capacity. After 14 days of germination, GSE was applied as a foliar spray at different concentrations (0, 2, 4, 6, and 8 g/L) to mitigate the negative effects of salt stress (150 mM NaCl) on faba bean plants. Foliar application of 2-8 g/L GSE significantly enhanced growth parameters such as shoot length, root length, fresh weight, and dry weight of salt-stressed bean plants compared to the control. The Fv/Fm ratio, indicating photosynthetic activity, also improved with GSE treatment under salinity stress compared to the control. GSE effectively alleviated the oxidative stress induced by salinity, reducing malondialdehyde, hydrogen peroxide, praline, and glycine betaine levels. Total soluble proteins, amino acids, and sugars were enhanced in GSE-treated, salt-stressed plants. GSE treatment under salinity stress modulated the total antioxidant capacity, antioxidant responses, and enzyme activities such as peroxidase, ascorbate peroxidase, and polyphenol oxidase compared to salt-stressed plants. Gene expression analysis revealed GSE (6 g/L) upregulated photosynthesis (chlorophyll a/b-binding protein of LHCII type 1-like (Lhcb1) and ribulose bisphosphate carboxylase large chain-like (RbcL)) and carbohydrate metabolism (cell wall invertase I (CWINV1) genes) while downregulating stress response genes (ornithine aminotransferase (OAT) and ethylene-responsive transcription factor 1 (ERF1)) in salt-stressed bean plants. The study demonstrates GSE's usefulness in mitigating salinity stress effects on bean plants by modulating growth, physiology, and gene expression patterns, highlighting its potential as a natural approach to enhance salt tolerance.

Cytotoxicity Effects of Formulated Mangosteen Rind and Grape Seed Extract Against Vero Cells, Breast Cancer and Colon Cancer

Globally, cancer causes millions of deaths in addition to significant social and economic consequences. Even in cases when the level of tolerated therapy has not been reached to suppress the death rate and shorten the duration of survival for metastatic cancer patients, novel therapeutic strategies are being employed, including medications, biological molecules, and immune-mediated therapies. Traditional medical practices relied heavily on plant-derived natural compositions to treat a variety of illnesses. When science-based "modern" medicine first appeared, it was carefully studied if there was any scientific basis for using natural remedies derived from plants to cure ailments. Scientists continued, however, to search for the scientific foundations of medical plants, herbal remedies, and functional foods. Finding therapeutic plant-based active principles has led to significant advancements in the identification and use of natural chemicals for the treatment of many ailments in recent decades. Mangosteen rind extract and grape seed extract, both high in antioxidants, were mixed as a formulation to explore the cytotoxic effects on breast and colon cancer. The cytotoxicity of MCF-7 and MDA-MB-231 (breast cancer) and HT-29 (colon cancer) was investigated and compared to the standard (Doxorubicin). The findings of the cytotoxicity assays show that the addition of Mangosteen and grape seed extract to MTT assays gradually improved the inhibition of MCF-7, MDA-MB-231, and HT-29 cells. Mangosteen and grape seed extract treatment boosted the fraction of cells undergoing apoptosis in MCF-7, MDA-MB-231, and HT-29 cancer cell lines. Thus, the invitro study results of compounded mangosteen and grape seed extract revealed that they are effective anti-cancer, anti-fungal, anti-bacterial, and antioxidant agents.

Evaluation of antioxidant application on bond strength of composite resins to bleached enamel

Abstract Aim: This study aims to assess and evaluate the application of 10% sodium ascorbate, 5% green tea extract, 5% pomegranate peel extract, and 5% grape seed extract on shear bond strength of composite to bleached enamel. Materials and Methods: Sixty extracted human maxillary central incisors were randomly divided into seven groups. The enamel surface of these specimens was bleached with hydrogen peroxide (35%), except group VII (control group). Postbleaching, the specimens of group II were placed in artificial saliva for 2 weeks before restoration and the specimens of groups III and IV and groups V and VI underwent antioxidant application; 10% sodium ascorbate, 5% green tea extract, 5% pomegranate peel extract, 5% grape seed extract, respectively, for 10 min, followed by composite resin restoration, respectively. The specimens of group I were restored with composite resin immediately after bleaching. The specimens’ shear bond strength was tested using universal testing equipment. The data obtained were statistically analyzed using a one-way analysis of variance and the Tukey post hoc test. Results: There was no statistically significant difference in the effects of various antioxidants on the shear bond strength of bleached enamel. Conclusion: Within the constraints of the study, it was concluded that the application of antioxidants efficiently recovered the bond strength of bleached enamel. The application of 5% grape seed extract treatment demonstrated better bond strength among the antioxidants tested. Clinical Significance: Antioxidants can be used immediately following bleaching to restore resin composite bond strength without the requirement of delay in the treatment to reduce the nascent oxygen species in bleached teeth.

Extracts of Dunkelfelder Grape Seeds and Peel Increase the Metabolic Rate and Reduce Fat Deposition in Mice Maintained on a High-Fat Diet.

Chronic high-fat diet intake may induce obesity and increase the risk of metabolic syndrome. The pomace of grape (Vitis vinifera L.) is rich in polyphenols, which are candidates for anti-obesity therapy. The present study aimed to investigate the effects of Dunkelfelder grape seed extract (GSE) and grape peel extract (GPE) on lipid and energy metabolism disorders in mice maintained on a high-fat diet (HFD). Male nine-week C57BL/6J mice were randomly assigned to one of four groups, namely, the normal chow diet (ND), HFD, HFD plus GSE (400 mg/kg BW) administered by oral gavage, or HFD plus GPE (400 mg/kg BW) administered by oral gavage. There were eight mice per group, and the experiment was 14 weeks in duration. The results showed that GSE and GPE treatments did not affect energy intake in mice on a high-fat diet, but body weight gain was 24.5% and 17.3% lower in the GSE- and GPE-treated mice than in the HFD group, respectively. They also decreased blood triglyceride (TG), total cholesterol (TC), and fasting blood glucose levels and increased high-density lipoprotein cholesterol (HDL-C). In addition, GSE and GPE reduced adipose tissue weight and excessive lipid droplet accumulation in the adipocytes. The metabolic chamber test showed that the GSE and GPE treatments enhanced oxygen consumption, carbon dioxide production, and heat release while decreasing the respiratory exchange rate (RER). This suggests that GSE and GPE augmented fuel oxidation and energy generation and increased the proportion of lipids being utilized in energy metabolism. GSE and GPE also upregulated the genes controlling lipolysis and downregulated those controlling lipogenesis in adipose tissues. Moreover, they significantly increased the expression levels of the genes regulating thermogenesis in BAT, eWAT, and iWAT, and mitochondrial biogenesis in all three types of adipose tissue. In conclusion, the present study empirically demonstrated that GSE and GPE enhance body fat utilization by augmenting lipid and energy metabolism and could, therefore, ameliorate high-fat diet-induced obesity.

Heated and unheated lupin protein‐grape seed extract conjugates stabilizing and structuring high internal phase oil‐in‐water emulsions

AbstractPlant‐based high internal phase oil‐in‐water emulsions (HIPEs) are promising fat replacers. However, producing stable HIPES with improved viscoelastic properties is a challenge for the food industry. Conjugation of plant proteins, such as lupin protein isolate, with phenolic compounds, such as proanthocyanidins from grape seed extract, associated (or not) with moderate heat treatment arise as potential methods to tune the surface properties of proteins and, consequently, the droplet‐droplet interactions that drive the viscoelastic properties of HIPEs. In this way, unheated (UHC) and heated (85°C, 15 min) (HC) lupin protein (LPI)‐grape seed extract (GSE) conjugates were produced and used to stabilize HIPEs. Evaluation of stability by Turbiscan and oil loss by centrifugation over 56 days of storage did not reflect the kinetic stability of HIPEs against process conditions. Under shearing, UHC‐stabilized emulsions at high GSE concentrations showed oil release, whereas all HC‐stabilized HIPEs released oil. However, the increase in GSE concentration and heat treatment improved the viscosity and storage modulus (G′) of HIPEs, possibly due to the droplet‐droplet interaction originating from hydrophilic and hydrophobic interactions in UHC and HC‐stabilized HIPEs, respectively. This pivotal study confirmed that conjugation of a plant protein with GSE and heat treatment could improve the viscoelastic properties of HIPEs and produce HIPEs with superior texture (higher G′).

Dietary effect of grape (Vitis vinifera) seed extract mitigates hepatic disorders caused by oxidized fish oil in rainbow trout (Oncorhynchus mykiss)

The major goal of this study was to determine the effect of grape seed extract (GSE) on liver damage in rainbow trout (Oncorhynchus mykiss) that was caused by the consumption of dietary oxidized fish oil (OFO). Rainbow trout were fed six different experimental diets coded OX-GSE 0 (OFO diet), OX-GSE 1 (OFO and 0.1% GSE), OX-GSE 3 (OFO and 0.3% GSE), GSE 0 (fresh fish oil and 0.0% GSE), GSE 1 (fresh fish oil and 0.1% GSE), and GSE 3 (fresh fish oil and 0.3% GSE) for 30days. The lowest % hepatosomatic index (HSI) result was calculated in fish fed with OX-GSE 0 and the highest HSI was determined in fish fed with GSE 1 diets (p < 0.05). Histopathologically, hydropic degeneration in hepatocytes significantly increased OX-GSE 0 and GSE 3 compared to GSE 1 diets (p < 0.05). Deposition of lipid droplets in hepatocytes was significantly increased in OX-GSE 0 and OX-GSE 3 groups than others (p < 0.05). Liver biochemistry parameters such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were significantly affected by OX and GSE treatments (p < 0.05). There were significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) among the liver enzymes analyzed in serum in OX and GSE (p < 0.05), meanwhile no difference was observed in lactate dehydrogenase (LDH) values between groups (p > 0.05). In conclusion, liver biochemistry and histopathology of rainbow trout consuming diets containing oxidized fish oil were negatively affected. However, it was determined that the supplementation of 0.1% GSE to the diet had a significant ameliorative role in these adverse effects.

Grape seed extract improves intestinal barrier integrity and performance: Evidence from in vitro, Caenorhabditis elegans and Drosophila melanogaster experiments and a study with growing broilers

Grape seed extract (GSE) is an interesting source for polyphenols and other phytochemicals with high antioxidant potential. Here, we report on a comprehensive study investigating GSE in various in vitro and in vivo experiments. Obtained results indicate that GSE improves parameters related to intestinal barrier integrity in cell culture, C. elegans and D. melanogaster. Faster wound healing was observed in a scratch assay using intestinal IPEC-J2 cells when pre-treated with GSE. Furthermore, reactive oxygen species were found to be significantly decreased in cell culture and C. elegans experiments. In C. elegans, qPCR gene expression analysis revealed significant modulations after 24 h of GSE treatment. Finally, a 42-day broiler feeding study revealed a dose dependant effect on growth performance in the GSE supplemented groups. In conclusion, GSE was found to provide promising properties including wound closure, intestinal integrity, and antioxidant activity.

Inhibitory Effects and Mechanism of Grape Seed Extract Treatment on Penicilliosis of Postharvest Kiwifruit

Inhibitory Effects and Mechanism of Grape Seed Extract Treatment on Penicilliosis of Postharvest Kiwifruit

Sensing of oxidative stress biomarkers: The cardioprotective effect of taurine & grape seed extract against the poisoning induced by an agricultural pesticide aluminum phosphide

Aluminum phosphide is a well-known hazardous agent used as an agricultural pesticide to protect stored grains from insect damage. However, accidental consumption of a trivial amount of it caused irreversible damage to the human body or even death in acute cases. The present study used taurine and grape seed extract as a natural cardioprotective medicine against aluminum phosphide poisoning by decreasing oxidative stress. The activity of oxidative stress biomarkers (Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase) were evaluated in the cell line model on Human Cardiac Myocyte cells. In the beginning, to clarify the pure impact of aluminum phosphide poison, taurine, and grape seed extract on the human heart cells, their effects on the biomarkers quantity in cell line were measured. Subsequently, the effect of taurine and grape seed extract with various concentrations as a treatment on the oxidative stress biomarkers of the poisoned heart cells were studied. Data analysis reveals that taurine and grape seed extract treatment can successfully diminish the poisoning effect by their antioxidant properties. The oxidative markers values of the poisoned cells were recovered by taurine and grape seed extracts treatment. Taurine (2 g/l) can recover Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase by 56%, 78%, 88%, 78%, when the recovering power of grape seed extract (100 g/l) for the aforementioned enzymes are 56%, 0.71%,74%, 51%, respectively. Therefore, it is clear that the performance of taurine in the recovery of the biomarkers’ value is better than grape seed extract.

Adjunction of the Lipase Inhibitor Orlistat Improves Grape Seed Extract Neuroprotection against Brain Ischemia/Reperfusion Injury in Rats

Abstract: Aim: Stroke is a public health concern for which there is currently no prophylaxis. In this study, we assessed the protective effect of Grape Seed Extract (GSE) and Orlistat (ORL) against brain ischemia/reperfusion (I/R) injury. Methods: Adult male Wistar rats were treated either with GSE (2.5 g/kg), ORL (4 mg/kg) or both drugs for one week and ischemia performed during 30 min by a bilateral common carotid artery occlusion (BCCAO), followed by 60 min reperfusion. Rats were then sacrificed, their whole brain used for infarct size determination using TTC staining or dissected into cortex, hippocampus and cerebellum for biochemical analysis of I/R-induced oxidative stress and energy failure. Results: In the three brain regions of interest, I/R disturbed protein carbonylation, xanthine oxidase (XO), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, as well as intracellular mediators as hydrogen peroxide (H2O2), calcium and iron. Furthermore I/R altered energy fueling through the decrease of α-ketoglutarate dehydrogenase (α-KGDH) and fumarase (FH) together with mitochondrial complexes I and II along with glutamatergic excitotoxicity through glutamate dehydrogenase (GDH) and glutamine synthetase (GS) activities into cortex and hippocampal areas but not into cerebellum. In addition I/R affected mitochondrial viability as assessed by MTT staining and the moonlighting apoptosis inducer glyceraldehyde-3- phosphate dehydrogenase (GAPDH). Conclusion: Interestingly, GSE prevented efficiently the deleterious effects of I/R and the best protection was obtained when combining the two drugs, especially within cortex and hippocampus compartments. Thus, adjunction of ORL to GSE treatment is a promising strategy to improve neuroprotection from stroke. Key words: Brain I/R, GSE, Orlistat, Neuroprotection, Energy failure.

Effect of grape seed extract on quality and microbiota community of container-cultured snakehead (Channa argus) fillets during chilled storage

Herein, the effects of grape seed extract (GSE) on the microflora and biochemical changes of container cultured snakehead (Channa argus) fillets during 11 days of chilled storage were investigated. The sensory analysis, the total number of viable colonies, the total amount of volatile basic nitrogen, and k-value analysis revealed that GSE retarded the deterioration of snakehead fillets. The degradation of inosine 5′-monophosphate and the accumulation of inosine and hypoxanthine in the GSE group were slower than these in the control group. Moreover, GSE treatment effectively decreased the accumulation of putrescine, cadaverine, and histamine. Illumina-MiSeq high throughput sequencing results showed that GSE inhibited the growth of Aeromonas on snakehead fillets. Based on the microbial enumeration, sensory analysis, and k-value, GSE prolonged the shelf life of fillets for 3 days, suggesting its potential for snakehead fillets preservation.

Renal protective effects of grape seed extract treatment against Eltroxin-induced hyperthyroidism, kidney damage, and oxidative stress in male mice.

The present study aimed to investigate the influence of grape seed extract (GSE) in renal toxicity, oxidative stress, and Bcl-2 expressions in Eltroxin-induced hyperthyroidism to male mice. GSE was evaluated through oral administration to male mice at dose 50mg/kg daily for 3 consecutive weeks. Eltroxin (100μg/kg) was administered to mice for 3weeks, and the mice were posttreated with GSE for another 3weeks. Results revealed that GSE administered to normal mice did not produce any signs of toxicity and did not cause any biochemical or histopathological changes. Posttreatment of Eltroxin-induced hyperthyroidism mice with GSE daily for 3weeks improved all examined biochemical or histopathological features. Oral GSE can significantly normalize the elevated level of T3 and T4 in hyperthyroidism animals and elevated the reduced levels of TSH. Moreover, serum urea, creatinine, and electrolyte levels were significantly improved. GSE showed a potent antioxidant capacity in all oxidative stress markers assays (TBARS, reduced GSH, GST, SOD, and CAT) of kidney tissue homogenates. Furthermore, histopathological examination of kidney tissue of Eltroxin + GSE-treated group confirms the potential nephroprotective effect of GSE through increasing the anti-apoptotic marker Bcl-2.

Effects of grape seed extract on performance, immunity, antioxidant capacity, and meat quality in Pekin ducks

This study was conducted to evaluate the effects of grape seed extract (GSE) on growth performance, immunity, antioxidant capacity, relative organ weight, jejunum morphology, ileal microflora, and meat quality in Pekin ducks. A total of 1,500 female 1-day-old Pekin ducklings (52.0 ± 0.2 g) were blocked based on body weight (BW) and randomly allocated into 3 treatments with 10 replicates of 50 birds each. The experiment lasted for 6 wk, and dietary treatments included corn-soybean meal-based diet supplemented with 0, 0.01, and 0.02% GSE. The supplementation of GSE increased (P < 0.05) body weight gain (BWG) and final BW linearly but decreased (P < 0.05) feed-to-gain ratio (F/G) linearly during day (D) 22 to 42 and the entire experiment. The inclusion of GSE increased (P < 0.05) serum superoxide dismutase, glutathione peroxidase, total antioxidative capacity, catalase, complement4, immunoglobin G, interleukin-2, and interferon-γ linearly but decreased (P < 0.05) serum malondialdehyde linearly. The relative weight of carcass, breast meat, and spleen in GSE treatments was increased (P < 0.05) linearly, whereas the relative weight of abdominal fat was decreased linearly (P < 0.05). Birds fed GSE1 and GSE2 diets had lower (P < 0.05) cook loss, 2-thiobarbituric acid reactive substances, and drip loss on day 3 and 5 linearly but higher (P < 0.05) pH24h and water-holding capacity. The addition of GSE decreased (P < 0.05) jejunum crypt depth and ileal Escherichia coli counts linearly but increased (P < 0.05) jejunum villus height: crypt depth ratio and ileal Lactobacilli linearly. Taken together, the inclusion of GSE increased final BW and BWG, decreased F/G during day 22 to 42 and day 1 to 42, partially improved antioxidant activities, immunity, meat quality, and gut health in Pekin ducks.

Upregulation of Antioxidant Gene Expressions and Enzyme Activity Against Acrylamide-Induced Neurotoxicity in Mice after Grape Seed Extract Treatment

Background: The risk of occupational exposure to acrylamide is high and long-term acrylamide exposure can cause neurotoxicity. Thus, therapeutic agents that can protect against acrylamide-induced neurotoxicity are needed. Objective: To investigate whether Grape Seed Extract (GSE) protects against acrylamide-induced neurotoxicity in mice. Methods: Mice were divided into saline, GSE, acrylamide, GSE followed by acrylamide, acrylamide followed by GSE, and simultaneous acrylamide and GSE treatment groups. Gene expression and antioxidant enzyme levels were then determined using RT-PCR and biochemical assays. Results: Gpx1 (P &lt; 0.05), Prdx3 (P &lt; 0.01), SOD1 (P &lt; 0.05), and CAT (P &lt; 0.05) significantly upregulated in GSE-treated mice, compared to those in untreated controls. In contrast, Gpx1 (P &lt; 0.05), Prdx3 (P &lt; 0.05), SOD1 (P &lt; 0.05), and CAT (P &lt; 0.05) significantly downregulated in acrylamide-treated mice compared to those in untreated controls. Results of the treatment with GSE before exposure to acrylamide or simultaneously with acrylamide indicated that GSE restored Gpx1, Prdx3, SOD1, and CAT expression to similar levels as those in the control group. GSE treatment after exposure to acrylamide did not exert any neuroprotective effects against acrylamide, as revealed by significant downregulation of Gpx1 (P &lt; 0.05), Prdx3 (P &lt; 0.01), SOD1 (P &lt; 0.05), and CAT (P &lt; 0.05) compared to that in untreated controls. Animals treated with grape seed before acrylamide treatment showed no significant change in LPO activities and a significant increase in GSH levels, compared to those in untreated controls. Conclusion: GSE exerted neuroprotective effects against acrylamide-induced neurotoxicity. Acrylamide caused oxidative stress 20 days post-exposure. However, grape seed treatment before exposure to acrylamide restored all test parameters to levels similar to control values.

Vitis Vinifera L.: A new bioactive anticandidal agent to combat oral candidal carriage in Down syndrome patients.

Down syndrome (DS) patients have a high risk of opportunistic infections from Candida species. Therefore, the purpose of this research was to assess the prevalence of Candida species in oral cavity of DS patients and investigating of grape seed extract (GSE) as a potential anticandidal agent. Our study included fifty patients with DS and fifty healthy children. Oral tongue swabs were taken from both groups and isolated Candida species were identified. The anticandidal activity of GSE against isolated Candida was studied using agar well diffusion method. Scanning electron microscope (SEM) was used to determine the major alterations in Candida after GSE treatment. GSE was subjected to GC-MS analysis and HPLC analysis. Forty six samples showed growth of Candida in DS group, where as ten samples in control group. The most common pathogenic Candida isolated from DS patients was C.tropicalis (65.2%). GSE showed significant inhibitory activity against C.tropicalis (MIC 30 mg/ml). The SEM showed complete alterations in Candida cell morphology. GC-MS chromatogram of GSE revealed 30 compounds, the major one is (9, 12-Octadecadienoic acid) which confirmed by HPLC chromatogram with a peak at RT 20.311 min. GSE could be a promising anticandidal agent and it may form a primary platform for further toxicological assessment and development of new drugs.

Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells.

Background and purpose:Ovarian cancer is the deadliest cancer in women. The main challenge in the inhibition of ovarian cancer cells is chemo-resistance. Seeking to overcome this issue, several strategies have been suggested, including the administration of natural products. Grape seed extract (GSE) is a good source of polyphenols and its anticancer effects have been reported by many studies. In this study we aimed to evaluate the effects of GSE on OVCAR-3, a chemo-resistant ovarian cancer line.Experimental approach:OVCAR-3 cells were treated with GSE (71 μg/mL) for 24 and 48 h. Cell viability and cell apoptosis were measured by MTT and flow cytometry. The real-time polymerase chain reaction was used to determine the expression of genes involved in the cell cycle (PTEN, DACT1, AKT, MTOR, GSK3B, C-MYC, CCND1, and CDK4) and apoptosis (BAX, BCl2, CASP3, 8 and 9). The expression of CASP3 protein was evaluated by the CASP3 assay.Findings / Results:The results showed that treatment of OVCAR-3 cells with GSE, increased the expression level of PTEN and DACT1 tumor suppressor genes, as well as apoptotic genes, CASP3, 8, and 9 (P < 0.001). Also, the induction of tumor suppressor genes expression was associated with an increase in the expression of BAX/BCL2 gene ratio as pro- and anti-apoptotic genes. The expression of the genes involved in the cell cycle, CCND1 and CDK4, was inhibited (P < 0.001). The results indicated that GSE induced cell apoptosis in a time-dependent manner (P < 0.001). Also, the GSE treatment resulted in the CASP3 protein expression (P < 0.001).Conclusion and implications:According to the results of this study, GSE may exert anti-tumorigenic effects on chemo-resistant OVCAR-3 ovarian cancer cells which might be mediated by the expression of tumor suppressor genes that interact with cell signaling pathways, cell cycle, and cell apoptosis. Hence, the consumption of GSE extract during chemotherapy may overcome part of chemo-resistance in ovarian cancer.

Effects of Grape Seed Extract and Proanthocyanidin B2 on In Vitro Proliferation, Viability, Steroidogenesis, Oxidative Stress, and Cell Signaling in Human Granulosa Cells.

Reactive oxygen species (ROS) which lead to oxidative stress affect ovarian function. Grape seed extract (GSE) could be proposed as an effective antioxidant, particularly due to its proanthocyanidin content. In this study, we investigated a dose effect (0, 0.01, 0.1, 1, 10, 50, and 100 μg/mL) of GSE and proanthocyanidin B2 (GSPB2) on the ROS content, cell proliferation, cell viability, and steroidogenesis in both primary luteinized granulosa cells (hGC) and the tumor granulosa cell line (KGN). The levels of ROS were measured using ROS-Glo assay. Cell proliferation and viability were evaluated by [3H]-thymidine incorporation and Cell Counting Kit-8 (CCK8) assay, respectively. Steroid secretion was evaluated by radioimmunoassay. We also analyzed the cell cycle component protein level and signaling pathways by immunoblot and the NOX4 mRNA expression by RTqPCR. From 0.1 to 1 μg/mL, GSE and GSBP2 reduced the ROS cell content and the NOX4 mRNA levels, whereas, GSE and GSBP2 increased the ROS cell content from 50 to 100 μM in both hGC and KGN. GSE and GSPB2 treatments at 50 and 100 μg/mL induced a delay in G1 to S phase cell cycle progression as determined by fluorescence-activated cell sorting. Consequently, they reduced cell growth, cyclin D2 amount, and Akt phosphorylation, and they increased protein levels of p21 and p27 cyclin-dependent kinase inhibitors. These data were also associated with an increase in cell death that could be due to a reduction in Bcl-2-associated death promoter (BAD) phosphorylation and an increase in the cleaved-caspase-3 level. All these negative effects were not observed at lower concentrations of GSE and GSPB2 (0.01 to 10 μg/mL). Interestingly, we found that GSE and GSPB2 treatments (0.1 to 100 μg/mL) improved progesterone and estradiol secretion and this was associated with a higher level of the cholesterol carriers, StAR (steroidogenic acute regulatory protein), CREB (Cyclic adenosine monophosphate Response Element-binding protein), and MAPK ERK1/2 (Mitogen-Activated Protein Kinases Extracellular signal-Regulated Kinases 1/2) phosphorylation in both hGC and KGN cells. Taken together, GSE and GSPB2 (0.1–10 μg/mL) in vitro treatments decrease oxidative stress and increase steroidogenesis without affecting cell proliferation and viability in human granulosa cells.

Grape seed extract and chromium nicotinate reduce impacts of heat stress in Simmental × Qinchuan steers

To assess the impacts of grape seed extract (GSE) fed with or without chromium nicotinate (CN) on beef steers under heat stress conditions, 40 Simmental × Qinchuan steers (400 ± 10 days old; 410 ± 8.0 kg) were randomly assigned to one of four diets (n = 10 per group): basal diet (CON group); basal diet + 33 mg/day CN (CN group); basal diet + 65 mg/kg DM GSE (GSE group); and basal diet + 33 mg/day CN + 65 mg/kg DM GSE (CN + GSE group). This study was conducted in summer and the steers were housed in outdoor shaded pens (10 steers/pen) and fed individually. The experiment lasted for 35 days, the first 7 days for diet and housing condition adaptation. The amount of feed intake was recorded daily; individual bodyweight was recorded on Days 8, 22, and 36. On Day 36 before feeding, six steers per group were slaughtered for collection of blood and tissue samples. Average daily liveweight gain and dry matter intake of steers were increased by the GSE, CN, and CN + GSE treatments (P &amp;lt; 0.05). Dietary treatments increased the activities of glutathione peroxidase and total superoxide dismutase in plasma (P &amp;lt; 0.05) and plasma concentration of interleukin 10 on Days 22 and 36 (P &amp;lt; 0.05), whereas decreased plasma concentration of tumour necrosis factor-α on Day 22 (P &amp;lt; 0.05). Overall, supplementation of GSE alone or with CN had positive effects on the growth performance of steers under heat stress conditions.

Grape Seed Extract Exerts an Anti-Apoptotic Effect and Attenuates the Decrease in Striatal Tyrosine Hydroxylase in Rotenone-Treated Mice

The potential neuroprotective effect of grape seed extract (GSE) was evaluated in the rotenone-induced Parkinson’s disease in mice. Rotenone was administered at the dose of 1.5 mg/kg subcutaneously (sc) three times per week for 2 weeks alone or in combination with GSE at doses of 13.5 and 27 mg/kg, sc, daily. The control group received the vehicle. The brain levels of the lipid peroxidation product malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite), and paraoxonase-1 (PON-1) were determined. Histopathology, caspase-9 immunohistochemistry in different brain regions, and tyrosine hydroxylase immunoreactivity (TH-ir) in the substantia nigra were performed. Behavioral testing included rearing activity, locomotor activity, and stair test paradigms. Results indicated significantly increased lipid peroxidation and nitric oxide contents along with a significant decrease in GSH level and marked inhibition of PON-1 activity in the striatum and in the rest of the brain tissue in rotenone-treated mice. Rotenone caused significant decreases in rearing and locomotor activities and impaired motor strength. Treatment with GSE at 27 mg/kg resulted in decreased MDA and nitric oxide by 22.8%/17.9% and 38.5%/45.5%, respectively, in the striatum and the rest of the brain. GSH was increased by 20.8% and 26%, while PON-1 activity increased by 204% and 142.9% after GSE treatment in the striatum and in the rest of the brain tissue, respectively, compared with the corresponding rotenone control values. GSE given at 27 mg/kg almost completely corrected the decrease in motor activity and motor strength caused by rotenone. Neuronal degeneration and the increase in caspase-9 expression caused by rotenone in different brain regions as well as the loss of substantia nigra TH-ir were markedly reduced by GSE. These data indicate that GSE was effective in improving brain oxidative stress and in preventing the behavioral deficits and neurodegeneration induced by rotenone in the mouse brain. It is suggested that GSE might be useful as an adjunctive treatment in patients with Parkinson’s disease.

Grape Seed Extract Supplementation Attenuates the Blood Pressure Response to Exercise in Prehypertensive Men.

We tested the hypothesis that exaggerated pressor responses observed in prehypertensive males (N = 9) during dynamic exercise are attenuated following acute dietary supplementation with grape seed extract (GSE) (i.e., a single dose). Effects of placebo and GSE (300 mg) on systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), total vascular conductance (TVC), and rate × pressure product (RPP) in response to two submaximal cycling workloads (40% and 60% VO2peak) were compared 2 h after ingestion of GSE or placebo on different days, 1 week apart. Endothelial function was also evaluated using flow-mediated dilation (FMD). Placebo treatment had no effect on any of the variables. GSE supplementation attenuated MAP at both workloads (40% VO2peak: 115 ± 1 vs. 112 ± 2 mmHg; 60% VO2peak: 126 ± 2 vs. 123 ± 2 mmHg) and RPP at the lower workload. Conversely, SV, CO, and TVC were augmented during both workloads. FMD was augmented by GSE (18.9 ± 2.0 vs. 12.4% ± 2.0%). These findings indicate that in exercising prehypertensive males, a single dose of GSE reduces blood pressure, peripheral vasoconstriction, and work of the heart and enhances O2 delivery; effects that may be due, in part, to endothelium-dependent vasodilation. We propose that acute GSE treatment represents an intervention that may minimize potential increases in the risk of cardiovascular events during dynamic exercise in prehypertensives.