OBJECTIVES: Myringosclerosis is an irreversible pathological healing mechanism of the tympanic membrane which can result in the formation of sclerotic plaques. Antioxidant treatment is a recognised prevention therapy and coenzyme Q10 (CoQ10), lycopene, and grape seed extract (GSE), were used in this manner. METHODS: Forty-four Wistar rats were used in this experiment, and, following myringotomies, the animals were randomly divided into four groups. CoQ10, lycopene or GSE was administered orally to the respective groups, starting from the day of surgery. Otomicroscopy examination was performed on the 14th day. All tympanic membrane lesions were evaluated and compared otomicroscopically and histopathologically. RESULTS: The otomicroscopy and histopathological findings, compared against a control (saline) group, showed the CoQ10, lycopene, and GSE groups had statistically significant differences of degree of sclerosis (P<0.001). CONCLUSION: CoQ10, lycopene, and GSE were compared against a saline group and their antioxidative and anti-inflammatory effects were similar. The formation of myringosclerotic plagues after experimental myringotomy in rats significantly decreased and diminished after systemic administration of the three different antioxidant supplements.
Animals ; Grape Seed Extract ; Myringosclerosis* ; Rats ; Rats, Wistar ; Sclerosis ; Tympanic Membrane

Animals ; Atherosclerosis ; prevention & control ; Biflavonoids ; pharmacology ; Catechin ; pharmacology ; Grape Seed Extract ; pharmacology ; Humans ; Proanthocyanidins ; pharmacology

BACKGROUND/AIMS: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. METHODS: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. RESULTS: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. CONCLUSIONS: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE.
Animals ; Antioxidants ; Cytokines ; Dinoprostone ; Glutathione ; Grape Seed Extract ; Indomethacin ; Misoprostol ; Proanthocyanidins ; Rats ; Rats, Sprague-Dawley ; Seeds ; Ulcer ; Vitis

This study investigated the inhibitory effect of grape seed proanthocyanidin extract (GSPE) on selenite-induced cataract formation in rats and the possible mechanism. Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups: control group, model group, three GSPE groups (low dose, medium dose and high dose). Control group received subcutaneous injection of physiological saline. Model group was given subcutaneous injection of sodium selenite (20 μmol/kg body weight) on the postpartum day 10, and once every other day for consecutive three times thereafter. GSPE treated groups were respectively administered GSPE at doses of 50, 100, and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection (that was, on the postpartum day 8), and once daily for fourteen consecutive days thereafter. The opacity of lenses was observed, graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured. The lenses were analyzed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), calcium (Ca(2+)), nitric oxide (NO) and anti-hydroxyl radical ability (anti-OH(-)). The histomorphology of lenses was observed with HE staining under a light microscope. The levels of calpainII, and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR. The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group, and the achievement ratio of model group was 100%. As compared with model group, the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups. Moreover, we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes (SOD, CAT, GSH-PX) and anti-OH(-) ability, accompanied by a significant increase in the levels of MDA, NO, Ca(2+) as well as iNOS, and calpainII protein and mRNA expression. Administration of GSPE could dose-dependently preserve the activities of these antioxidative enzymes and anti-OH(-) ability, accompanied by a significant reduction in the levels of MDA, NO, Ca(2+) as well as iNOS, and calpainII protein and mRNA expression. These results suggested that GSPE markedly prevented selenite-induced cataract formation probably by suppressing the generation of lipid peroxidation and free radicals as well as the activation of iNOS, and calpainII in the lenses.
Animals ; Cataract ; chemically induced ; drug therapy ; Grape Seed Extract ; pharmacology ; Plant Extracts ; pharmacology ; Proanthocyanidins ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Selenious Acid ; adverse effects

The aim of the present study was to assess the anti-obesity effects of grape seed extract (GSE) supplement in C57BL/6J mice. Thirty mice were divided into three groups; normal diet control group (ND), high fat diet control group (HD) and high fat diet plus grape seed extract supplemented group (HD+GSE). Results were as follows: 1. GSE supplement reduced the weight gain in mice fed high fat diets; epididymal and back fat weights were lower compared to non-supplemented HD group. 2. Blood lipid concentrations were lower in the HD+GSE group than in the HD group. Serum HDL-C concentrations were higher in the HD+GSE group compared with the other groups. 3. The concentrations of acid-insoluble acylcarnitines (AIAC) in serum and liver were higher in the HD+GSE group than in the HD group. 4. GSE supplementation increased mRNA levels of lipolytic genes such as carnitine palmitoyltransferase-1 (CPT-1) and decreased mRNA levels of lipogenic genes such as acetyl CoA carboxylase (ACC). These findings suggest that grape seed extract supplements in high fat diet might normalize body weight, epididymal and back fat weights, lipid concentrations, and carnitine levels through controlling lipid metabolism.
Acetyl-CoA Carboxylase ; Animals ; Body Weight ; Carnitine ; Diet ; Diet, High-Fat ; Gene Expression ; Grape Seed Extract ; Lipid Metabolism ; Liver ; Mice ; Obesity ; RNA, Messenger ; Vitis ; Weight Gain ; Weights and Measures

The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing H2O2 that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia.
Animals ; Antioxidants ; Catalase ; Cats ; Cholesterol ; Diet ; Glutathione ; Glutathione Disulfide ; Glutathione Peroxidase ; Grape Seed Extract ; Hypercholesterolemia ; Lipid Peroxidation ; Liver ; Malondialdehyde ; Oxidative Stress ; Rabbits ; Seeds ; Vitis

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.
Animals ; Arsenic ; toxicity ; Grape Seed Extract ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; Kidney Diseases ; chemically induced ; drug therapy ; Male ; Mice ; Proanthocyanidins ; therapeutic use

OBJECTIVE: To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms. METHODS: The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects. RESULTS: GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 μg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 μg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination. CONCLUSION GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.
Apoptosis ; Cell Line, Tumor ; drug effects ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Grape Seed Extract ; pharmacology ; Humans ; MicroRNAs ; genetics ; metabolism ; Pancreatic Neoplasms ; pathology ; Proanthocyanidins ; pharmacology ; Up-Regulation

PURPOSE: Grape seed-derived polyphenols (GSPs) provide a concentrated source of polyphenols having antioxidant capacity. In this study we investigated the cytoprotective effect of GSP against oxidative stress-induced cell damage in cultured human retinal pigment epithelial (RPE) cells. METHODS: Cultured adult retinal pigment epithelium (ARPE)-19 cells were incubated with GSP from Vitis vinifera (0.1, 0.5, 1, 5 or 10 microg/mL) for 24 hours and treated with hydrogen peroxide (H2O2, 0.4 mM) for 24 hours to induce oxidative stress. Cell viability was measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Intracellular reactive oxygen species (ROS) was quantified using 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescence. RESULTS: The percentage of viable RPE cells was significantly lower in cultures treated with H2O2 0.4 mM than in control cultures. GSP significantly reduced H2O2-induced cell death in a dose dependent manner. GSP at 0.1, 0.5, 1, 5 and 10 microg/mL significantly reduced cell mortality due to the treatment with H2O2. Intracellular ROS production increased significantly in cultures treated with H2O2 0.4 mM compared with control. There was a significant dose-dependent decrease in intracellular ROS levels after treatment of RPE with GSP. CONCLUSIONS: GSP, a natural polyphenolic compound, can protect RPE cells from H2O2-induced oxidative stress and reduce intracellular ROS production by scavenging free radicals. This suggests potential effects of polyphenolic compounds against retinal diseases associated with oxidative stress.
Adult ; Cell Death ; Cell Survival ; Epithelial Cells* ; Fluorescence ; Free Radicals ; Grape Seed Extract ; Humans ; Hydrogen Peroxide ; Mortality ; Oxidative Stress* ; Polyphenols ; Proanthocyanidins ; Reactive Oxygen Species ; Retinal Diseases ; Retinal Pigment Epithelium ; Retinaldehyde* ; Vitis

OBJECTIVETo determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity.

METHODSSixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed.

RESULTSATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST.

CONCLUSIONGSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Animals ; Antioxidants ; metabolism ; Arsenic ; toxicity ; Grape Seed Extract ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Mice ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Proanthocyanidins ; pharmacology ; Signal Transduction ; drug effects ; Sperm Count ; Testis ; cytology ; drug effects ; metabolism