Winery by‑products as a feed source with functional properties:dose–response effect of grape pomace,grape seed meal,and grape seed extract on rumen microbial community and their fermentation activity in RUSITEC

Background Grape and winery by-products have nutritional values for cattle and also contain functional compounds like phenols,which not only bind to protein but can also directly affect microbiota and their function in the rumen.We characterized the nutritional and functional effects of grape seed meal and grape pomace as well as an effective dosage of grape phenols on ruminal microbiota and fermentation characteristics using a rumen simulation technique.Results Six diets(each n=8)were compared including a control diet(CON,no by-product),a positive control diet(EXT,CON+3.7%grape seed extract on a dry matter(DM)basis),two diets with grape seed meal at 5%(GS-low)and 10%(GS-high),and two diets with grape pomace:at 10%(GP-low)and 20%(GP-high),on a DM basis.The inclusion of the by-product supplied total phenols at 3.4%,0.7%,1.4%,1.3%,and 2.7%of diet DM for EXT,GS-low,GS-high,GP-low,and GP-high,respectively.Diets were tested in four experimental runs.All treatments decreased ammonia concentrations and the disappearances of DM and OM(P<0.05)compared to CON.EXT and GP-high lowered butyrate and odd-and branch-chain short-chain fatty acids while increased acetate compared to CON(P<0.05).Treatments did not affect methane formation.EXT decreased the abundance of many bacterial genera including those belonging to the core microbiota.GP-high and EXT consistently decreased Olsenella and Anaerotipes while increased Ruminobacter abundances.Conclusion The data suggest that the inclusion of winery by-products or grape seed extract could be an option for reducing excessive ammonia production.Exposure to grape phenols at a high dosage in an extract form can alter the rumen microbial community.This,however,does not necessarily alter the effect of grape phenols on the microbial community function compared to feeding high levels of winery by-products.This suggests the dominant role of dosage over the form or source of the grape phenols in affecting ruminal microbial activity.In conclusion,supplementing grape phenols at about 3%of diet DM is an effective dosage tolerable to ruminal microbiota.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty 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. Results ATO-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, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Inhibitory Effects of Grape Seed Proanthocyanidin Extract on Selenite-induced Cataract Formation and Possible Mechanism

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.

Neuroprotective Effects of Grape Seed Procyanidin Extracton Ischemia-Reperfusion Brain Injury

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 mm3 vs. 47.84±9.06 mm3, 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.

Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities

Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer’s disease(AD).Currently,there is no effective drug available for the treatment of AD.Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation.Grape seed proanthocyanidin extract(GSPE)has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage.This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)(ICV-STZ).Rats were treated with GSPE(50,100,or 200 mg/kg every day)by intragastrical(ig.)administration for continuous 7 weeks,and ICV-STZ(3 mg/kg)was performed on the first day and third day of week 5.Learning and memory abilities were assessed by the Morris water maze(MWM)test at week 8.After behavioral test,hippocampal long-term potentiation(LTP)was recorded,and the levels of malondialdehyde(MDA),superoxide dismutases(SOD),glutathione(GSH)and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats.Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats,significantly increased the levels of MDA,and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex.In contrast,GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ,decreased the level of MDA,and increased the level of SOD and GSH.Furthermore,Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ.Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities.Therefore,GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD.

Quantitative Mitochondrial Proteomics Study on Protective Mechanism of Grape Seed Proanthocyanidin Extracts Against Ischemia/Reperfusion Heart Injury in Rat

Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques

Background Atherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract （GSPE） has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use. Methods Consecu- tive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness （CIMT） were ran- domly assigned to the GSPE group （n = 146） or control group （n = 141）. The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was per- formed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT （MMCIMT）, plaque score, echogenicity of plaques and ischemic vascular events were recorded. Results As anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT pro- gression （4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months） and plaque score （10.9% de- crease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months） for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also de- creased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack （TIA）, arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower （P = 0.02, 0.08, 0.002, respectively） compared with the control group. Conclusions GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.

Effects of grape seed extract on meat color and premature browning of meat patties in high-oxygen packaging

This study investigated the effects of grape seed extract(GSE)on fresh and cooked meat color and premature browning(PMB)in ground meat patties(85% beef and 15% pork back fat)packaged under high-oxygen modified atmospheres(HiOx-MAP).The GSE was added to patties at concentrations of 0,0.10,0.25,0.50 and 0.75 g kg^(-1).This study evaluated the surface color,pH,lipid oxidation,and total viable counts(TVC)of raw patties,and the internal color and pH of patties cooked to a temperature of 66 or 71℃ over 10-day storage at 4℃.Compared with the control(0 g kg^(-1) GSE),GSE improved the color stability(P<0.05)and significantly inhibited the lipid and myoglobin oxidation of raw patties from day 5 to 10,but GSE had no effect(P>0.05)on TVC.Patties containing 0.50 and 0.75 g kg^(-1) GSE cooked to 66℃ exhibited greater(P<0.05)interior redness than the control and reduced the PMB of cooked patties in the late storage stage.These results suggested that 0.50 and 0.75 g kg^(-1) GSE can improve fresh meat color and minimize PMB of HiOx-MAP patties.

Grape Seed Procyanidin Extract Reduces Arsenic- Induced Renal Inflammatory Injury in Male Mice

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）-KB 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-KB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Effects of Olive Oil and Grape Seed Oil on Lipid Profile and Blood Pressure in Patients with Hyperlipidemia: A Randomized Clinical Trial

Background and Aims: Hyperlipidemia is one of clear risk factors of diabetes. Regarding its importance, this study was designed to compare the effects of olive oil and grape seed oil on serum lipids and blood pressure in patients with hyperlipidemia in 2015. Methods and Results: In this clinical trial, 60 patients with hyperlipidemia who met inclusion criteria were recruited. Subjects were randomly assigned 3 groups: 1) consume 20 ml/day refined olive oil;2) consume 20 ml/day grape seed oil;3) the control group received no oil. The study period was six weeks. All participants were under Step I diet. Height and weight measurements were taken by Seca scale. Blood pressure, total cholesterol, high-density lipoprotein, triglyceride and fasting blood sugar were measured at baseline and after 6 weeks by standard methods. Low-density lipoprotein levels were calculated by the Friedewald’s formula. Data were analyzed with ANOVA test in SPSS software version 16.0. Sixty participants (36 female and 24 male) with the average age of 47.5 ± 9 y and the mean body mass index of 31.78 ± 5.41 kg/m2 had completed the study. Olive oil intervention decreased systolic blood pressure significantly compared to grape seed oil group (P = 0.01). Triglyceride was significantly decreased in olive oil and also triglyceride groups (P = 0.02 and 0.004, respectively). Conclusion: Overall, the effects of olive oil and grape seed oil were better than control group. However, we suggest the substitution of dietary lipids with olive oil because of its more beneficial effects. Registration number for clinical trial: IRCT2014070218329N1 registration code in Iran Clinical Trial site.

In vitro Evaluating the Influence of Grape Seed Polyphenol Extract on the Digestibility of Macronutrients

Interaction between dietary polyphenol and proteins including digestive enzymes may result in reduced digestibility of food macronutrients, thus lowering absorption of nutrients that contributing to high energy accumulation in human body. The objective of this study was to investigate the effect of grape seed polyphenol extract （GSPE） on the digestibility of starch, food lipid and food protein by digestive enzymes such as u-amylase, lipase, pepsin and trypsin. The digestion of each substrate was conducted at the optimal pH and temperature of specific enzyme. Bread containing different amount of grape pomace was used as a real food model and its digestion was conducted under simulated digestion condition. Concentrations of reducing sugar, fatty acid and amino acids in enzyme digested mixtures were determined as indicators of starch, lipid and protein digestions, respectively. Results indicate that GSPE significantly inhibited the digestion of starch, cooking oil and casein, but did not inhibit digestion of whey protein and egg white protein. Instead, the digestion of egg white and whey protein by trypsin was moderately enhanced in the presence of GSPE. However, under simulated human digestion condition, the grape pomace in the bread significantly reduced the digestibility of bread starch and protein.

Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in liver cancer xenograft model

Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins(GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, Eph A2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar(4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups than in the control group(all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups(all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, Eph A2 and MMP-2 protein in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups when compared with control group(all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/Eph A2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.

Vitamin C, Grape Seed Extract and Citrus Bioflavonoids Protect the Skin against Photoaging: A Review

The skin is a major protective organ of the body. It is constantly exposed to the environment and is very resilient. But exposure to ultraviolet (UV) rays from the sun results in the production of reactive oxygen species (ROS) and subsequent inflammatory responses that can overwhelm the innate protective mechanisms of the skin. This results in damage and premature aging. Strategies to mitigate this premature photoaging might include avoidance of sunlight. However, some sunlight exposure is beneficial to health. One notable example of this is the production of vitamin D. A more practical approach to preventing adverse effects of UV light in the skin is antioxidant supplementation. Dietary antioxidants may help control ROS propagation following UV light exposure. To further evaluate the utility of antioxidants in protecting the skin, in vitro, in vivo and human studies of three well known dietary antioxidants are reviewed and discussed. The data clearly demonstrate that vitamin C, grape seed extract and citrus bioflavonoids have the potential to reduce the damaging effects of excess sun exposure via antioxidant, anti-inflammatory and immunomodulating mechanisms. As such, regular ingestion of dietary antioxidants appears to be a useful strategy for protecting the skin against photoaging.

Role of survivin in apoptosis induced by grape seed procyanidin extract in human bladder cancer BIU87 cells

Objects： The aim of this study was to research the effect of grape seed procyanidin extract （GSPE） on cell apotosis in human bladder cancer BIU87 cells and investigate its molecular mechanism. Methods： BIU87 cells were treated with different concentrations of GSPE and cultured for 24 h in vitro while untreated group as control, MTT[3- （4,5-dimethylthiazole- 2-yl） -2, 5-diphenyltetrazolium bromide] assay, Hoechst 33258 stainning, flow cytometry, RT-PCR and Western blot were used to detect the apoptotic induction effect of GSPE on BIU87 cells. Results： We found that GSPE induced cell apoptosis in BIU87 cells by a dose-dependent manner. Semiquantitated RT-PCR and Western blot analyses indicated that GSPE increased the expression of caspase-3 and decreased the expression of survivin （P 〈 0.01）. Conclusion： GSPE induces apoptosis in BIU87 cells in vitro, and the effect maybe related with its down-regulation of survivin.

Effects of Grape Seeds and Tea Polyphenols on Serum Enzymatic Indices of Finless Eels ( Monopterus albus )

[Objectives]This study was conducted to investigate the possibility of adding grape seeds and tea polyphenols to improve the health of finless eels(Monopterus albus).[Methods]Twelve cages were selected in the same water body and divided into 4 groups,each with 3 parallel groups.The control group was fed with common finless eel feed,and the experimental groups were fed with feed supplemented with grape seeds,tea polyphenols,and grape seed-tea polyphenol compound(with a ratio of grape seeds to tea polyphenols at 1∶1),respectively.The feeding amount of each additive was 1%.The experiment was carried out by feeding medicated feed for 3 d and ordinary feed for 3 d,that is,alternately feeding medicated feed and ordinary feed.The experiment lasted for 18 d.[Results]Six serum enzymatic indices were detected after the breeding.The results showed that compared with the control group,the three groups of samples had a certain protective effect on the liver in terms of liver function indices.In terms of immunity evaluation,the tea polyphenol group and the grape seed-tea polyphenol complex group could increase the immunity of eels to varying degrees.In terms of antioxidant capacity,all three groups of samples could increase the body's antioxidant capacity.The results of this study showed that adding tea polyphenols and grape seeds to the feed simultaneously could effectively protect the liver of fish,and simultaneously enhance their antioxidant and non-specific immune functions.[Conclusions]This study provides a reference for the application of the two Chinese herbal medicines,grape seeds and tea polyphenols,in finless eel farming.

Grape Seed Extract and the Fetal Ductus Arteriosus: A Potential Danger of a Common Herbal Supplement

A female at 28 weeks gestation was referred to pediatric cardiology for a fetal arrhythmia. The echocardiogram revealed premature constriction of the fetal ductus arteriosus. Her work up was unremarkable except for her use of an herbal supplement, grape seed extract, which is advertised as a potent anti-inflammatory medication, and has biochemical properties similar to other medications that have been shown to cause premature ductal constriction. The use of herbal remedies increases each year. Although the public is inundated with radio, television, and internet advertisements for these products, little unbiased information regarding the possible dangers of toxicity or adverse reactions exists. As physicians, we need to be aware of these products, and counsel our patients accordingly.

Efficient semisynthetic approach for large preparation of procyanidin C1 through degradation of grape seed polymeric procyanidins

An efficient method for producing trimeric procyanidin C1(PCC1)was developed through degradation of grape seed polymeric procyanidins(PPCs),using epicatechin(EC)as nucleophile and hydrochloric acid as catalyst.With the yield of PCC1 as the evaluation index,the degradation conditions were optimized by Box-Behnken Design(BBD)based on the results of single-factor experiments.The results showed that the optimal conditions were reaction temperature of 40℃,the ratio of EC and PPCs 2:1,acidity of 0.10 mol/L,and reaction time of 20 min.The yield of PCC1 reached up to 17.7 mg by only one-step degradation of 3 g PPCs.This work proposed a new method for large preparation of PCC1 from waste grape seed polymeric procyanidins.

A review:anticancer activity of grape seed proanthocyanidins

For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.

Grape seed proanthocyanidin protects liver against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress

AIM: To explore the effect of grape seed proanthocyanidin(GSP) in liver ischemia/reperfusion(IR) injury and alleviation of endoplasmic reticulum stress.METHODS: Male Sprague-Dawley rats(220-250 g) were divided into three groups, namely, sham, IR, and GSP groups(n = 8 each). A liver IR(70%) model was established and reperfused for 6 h. Prior to reperfusion, the GSP group was administered with GSP(100 mg/kg) for 15 d, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase and methane dicarboxylic aldehyde were detected. Western blot was conducted to analyze the expression of glucoseregulated protein 78, CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb. Apoptotic cells were detected by TUNEL staining.RESULTS: The serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the IR group(P s < 0.05). The methanedicarboxylic aldehyde level was decreased in the GSP group, but the superoxide dismutase level was reversed(P s < 0.05). Similarly, GSP downregulated the proinflammatory factors and upregulated the levels of anti-inflammatory factors(Ps < 0.05). Western blot data showed that GSP increased glucose-regulated protein 78 expression and suppressed expression of CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb compared with the IR group.CONCLUSION: GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving endoplasmic reticulum stress through regulation of related signaling pathways to protect the liver against IR injury.

In vitro antimicrobial effects of grape seed extract on peri-implantitis microflora in craniofacial implants

Objective:To determine the antimicrobial effects of grape seed on peri-implantitis microflora.Methods:The 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.Results:Grape seed extract showed positive inhibitory effects with S.aureus at MIC of 0.625 mg/mL and MCC of1.25 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.Conclusions:The 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 skinabutment interface of craniofacial implants.