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

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

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

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 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

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

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

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

Objective Oxidative stress (OS) plays a crucial role in ischemic stroke. Grape seed procyanidin extract (GSPE) was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury.Methods Transient middle cerebral artery occlusion (MCAO) was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE (MCAOG, n=60) or normal saline (MCAONS, n=60). Sham-operated mice (GSPE group and normal saline group) were set as controls. The neurological severity score (NSS) was used to evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion, and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen (NeuN), CD34, Bcl-2, and Bax. Glutathione peroxidation (GSH-Px) activity and the level of malonaldehyde (MDA) of brain tissue were also examined. The above indexes were compared among the groups statistically.Results Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group (P<0.05). MCAOG group had smaller cerebral stroke volume (22.46 ± 11.45 mmvs. 47.84±9.06 mm, P<0.05) than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice (both P<0.05). MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG (P<0.05). The mean MDA level was significantly lower (P<0.05) and the GSH-Px activity was significantly higher (P<0.05) in brains of MCAOG mice compared to those of MCAONS mice.Conclusion GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis, promoting angiogenesis, and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.
Animals ; Apoptosis ; drug effects ; Brain ; blood supply ; Glutathione Peroxidase ; metabolism ; Grape Seed Extract ; pharmacology ; Infarction, Middle Cerebral Artery ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; Proanthocyanidins ; pharmacology ; Reperfusion Injury ; drug therapy ; metabolism

OBJECTIVETo determine the antimicrobial effects of grape seed on peri-implantitis microflora.

METHODSThe grape seed extract was tested against peri-implantitis microflora most commonly found in craniofacial implants including reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Candida albicans (C. albicans) and clinical strains of S. aureus, Klebsiella pneumonia (K. pneumonia) and Candida parapsilosis (C. parapsilosis) by disk diffusion test. Minimum inhibitory concentrations (MIC) and minimum cidal concentrations (MCC) were determined using modified agar dilution millpore method. The extract was further combined with polyethylene glycol and propylene glycol, and was tested for antimicrobial effects.

RESULTSGrape seed extract showed positive inhibitory effects with S. aureus at MIC of 0.625 mg/mL and MCC of 1.25 mg/mL respectively. However the extracts showed minimal or no reactivity against strains of E. coli, K. pneumonia, C. parapsilosis and C. albicans. The use of grape seed extract in combination with polyethylene glycol and propylene glycol also showed dose dependent inhibitory effect on S. aureus.

CONCLUSIONSThe results of the study showed that grape seed has potential antimicrobial effects which can be further studied and developed to be used in the treatment of infected skin-abutment interface of craniofacial implants.

Anti-Infective Agents ; pharmacology ; Bacteria ; drug effects ; Craniofacial Abnormalities ; surgery ; Disk Diffusion Antimicrobial Tests ; Grape Seed Extract ; pharmacology ; Humans ; Microbial Sensitivity Tests ; Prostheses and Implants ; adverse effects ; Prosthesis-Related Infections ; drug therapy ; microbiology