Grape seed extract protects rat offspring hippocampus from the silicon dioxide nanoparticles' neurotoxicity.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-NPs transfer to the offspring's brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO2-NPs. After delivery, animals were administered 25 mg/kg SiO2-NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO2-NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring's hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Effects of dietary supplementation of grape seed extract in comparison with excessive level of vitamin E on growth performance and antioxidant function of broilers.

The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.

Antibacterial effect of red laser-activated silver nanoparticles synthesized with grape seed extract against Staphylococcus aureus and Escherichia coli.

Living organisms, particularly humans, frequently encounter microorganisms such as bacteria, fungi, and viruses in their surroundings. Silver nanoparticles are widely used in biomedical devices because of their antibacterial and antiviral properties. The study evaluates the efficacy of red laser and silver nanoparticles from grape seed extract (AgNPs-GSE) in reducing Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, which cause infections. The sample comprised three groups: a control group without laser irradiation (T0), Escherichia coli samples (A1 and A2) irradiated with a 405-nm diode laser at different times and concentrations of silver nanoparticles, and Staphylococcus aureus samples (A3 and A4) illuminated with a 405-nm diode laser at different times and concentrations. Bacteria in groups A2 and A4 were treated with a photosensitizer (PS) made from grape seed extracts, incubated for 10 min, and then irradiated for 90, 120, 150, and 180 s. The samples were cultured on TSA media, set at 37 °C, counted using a Quebec colony counter, and analyzed using ANOVA and Tukey tests with a significance level of p < 0.05. The study illustrated that the combination of 10 µl of AgNPs-GSE, exposure to a red laser at 405 nm, and an energy density of 3.44 J/cm2 effectively photoinactivated both Escherichia coli and Staphylococcus aureus bacteria. For Escherichia coli bacteria irradiated for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, bacterial viability decreased by 64.50%, 70.74%, and 79.53%, respectively. Similarly, Staphylococcus aureus bacteria, subjected to irradiation for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, demonstrated reductions in bacterial viability by 70.23%, 73.47%, and 85.04%, respectively. The findings from the present study indicate that at an energy density of 3.44 J/cm2, it was possible to inactivate Escherichia coli by 79.53% and Staphylococcus aureus by 85.04%.

Grape seed extract supplementation in non-alcoholic fatty liver disease.

Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there's a lack of studies on grape seed extract's (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 µM vs. 4.59±1.19 µM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. -0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. -12.0±37.5; 3.80±14.8 vs. -3.92±9.55; 5.08 5.26 vs. -7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study.

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.

Effect of flavonoids from grape seed and cranberry extracts on the microbiological activity of Streptococcus mutans: a systematic review of in vitro studies.

OBJECTIVE: To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans). METHODS: This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias. RESULTS: Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content. CONCLUSIONS: The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.

Can grape polyphenols affect glycation markers? A systematic review.

Advanced glycation end-products (AGEs) favor inflammation and oxidative stress, playing a role in chronic diseases pathogenesis. Grape polyphenols exert antiglycative and antioxidant effects which may contribute to prevent chronic diseases. However, clinical evidence of grape polyphenols on chronic disease prevention and treatment by glycation markers modulation are limited. Therefore, we aimed to critically analyze studies about that topic to investigate the antiglycative power of dietary grape polyphenol, and to explore the molecular mechanism involved. This systematic review was conducted and reported according to PRISMA guidelines. The following search terms were used: "grape", "extract", "grape seed extract", "grape skin extract", "polyphenol extract", "grape polyphenol(s)", "grape juice", "resveratrol", "quercetin", "catechin", "epicatechin", "procyanidin(s)", and "anthocyanin(s)". Seven studies were included. Glycated hemoglobin was not affected. The interventions duration may not have been enough to detect changes. Grape polyphenols reduced fructosamine and methylglyoxal (MGO) concentrations, and increased endogenous secretory RAGE (esRAGE) gene expression but did not affect the serum concentration. Resveratrol antiglycative effects are mainly due its ability to trap MGO and downregulate RAGE. In conclusion, grape polyphenols may have a positive impact on early glycation products, AGEs and esRAGE. Future studies are needed to explore how they modulate AGEs and receptors in chronic diseases.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks.

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8-21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

Root canal disinfection and maintenance of the remnant tooth tissues by using grape seed and cranberry extracts.

The purpose of this study was to perform an integrative review on the effects of cranberry and grape seed extracts concerning the disinfection of root canals maintaining the strength of the remnant tooth tissues' structure. A bibliographical search was carried out on the PubMed electronic platform using the following key terms: cranberry, grape seed, vaccinium macrocarpon, proanthocyanidin, antibacterial, antimicrobial, decontamination, disinfection, bacteria removal, bacteria eradication, bacteria elimination, endodontic, root canal, faecalis, and strength. The inclusion criteria involved articles published in the English language, until March, 2022, reporting the antibacterial effect of grape seed and cranberry extracts. Of 185 studies identified, 13 studies were selected for the present review. The grape seed extract (GSE), composed of proanthocyanidins, showed an antioxidant activity against the main bacteria found in endodontic secondary infection. The percentage of bacteria removal was recorded at around 96.97% by using GSE. Studies on cranberry extracts, which are composed of proanthocyanidins, revealed antimicrobial effects against bacteria related to periodontitis and dental caries. Additionally, GSE or cranberry allowed the dentin collagen cross-linking that preserved the 3D collagen network leading to the maintenance of the strength of the remnant tooth structure. However, the contaminated smear layer could not be removed by using only GSE or cranberry. Cranberry extracts and GSE revealed a significant antimicrobial activity in endodontic disinfection without changing the mechanical properties of the remnant dentin tissues. Furthermore, those components can be associated with traditional compounds to enhance their antimicrobial effects and eliminate the smear layer.

Stearoyl-CoA Desaturases1 Accelerates Non-Small Cell Lung Cancer Metastasis by Promoting Aromatase Expression to Improve Estrogen Synthesis.

Metastases contribute to the low survival rate of non-small cell lung cancer (NSCLC) patients. Targeting lipid metabolism for anticancer therapies is attractive. Accumulative evidence shows that stearoyl-CoA desaturases1 (SCD1), a key enzyme in lipid metabolism, enables tumor metastasis and the underlying mechanism remains unknown. In this study, immunohistochemical staining of 96 clinical specimens showed that the expression of SCD1 was increased in tumor tissues (p < 0.001). SCD1 knockdown reduced the migration and invasion of HCC827 and PC9 cells in transwell and wound healing assays. Aromatase (CYP19A1) knockdown eliminated cell migration and invasion caused by SCD1 overexpression. Western blotting assays demonstrated that CYP19A1, along with ß-catenin protein levels, was reduced in SCD1 knocked-down cells, and estrogen concentration was reduced (p < 0.05) in cell culture medium measured by enzyme-linked immunosorbent assay. SCD1 overexpression preserving ß-catenin protein stability was evaluated by coimmunoprecipitation and Western blotting. The SCD1 inhibitor A939572, and a potential SCD1 inhibitor, grape seed extract (GSE), significantly inhibited cell migration and invasion by blocking SCD1 and its downstream ß-catenin, CYP19A1 expression, and estrogen concentration. In vivo tumor formation assay and a tail vein metastasis model indicated that knockdown of SCD1 blocked tumor growth and metastasis. In conclusion, SCD1 could accelerate metastasis by maintaining the protein stability of ß-catenin and then promoting CYP19A1 transcription to improve estrogen synthesis. SCD1 is expected to be a promised therapeutic target, and its novel inhibitor, GSE, has great therapeutic potential in NSCLC.

Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders.

(1) Background: DA-Gelucire® 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson's disease (PD) treatment. To develop powders constituted by such SLNs for nasal administration, herein, two different agents, namely sucrose and methyl-ß-cyclodextrin (Me-ß-CD), were evaluated as cryoprotectants. (2) Methods: SLNs were prepared following the melt homogenization method, and their physicochemical features were investigated by Raman spectroscopy, Scanning Electron Microscopy (SEM), atomic force microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS). (3) Results: SLN size and zeta potential values changed according to the type of cryoprotectant and the morphological features investigated by SEM showed that the SLN samples after lyophilization appear as folded sheets with rough surfaces. On the other hand, the AFM visualization of the SLNs showed that their morphology consists of round-shaped particles before and after freeze-drying. XPS showed that when sucrose or Me-ß-CD were not detected on the surface (because they were not allocated on the surface or completely absent in the formulation), then a DA surfacing was observed. In vitro release studies in Simulated Nasal Fluid evidenced that DA release, but not the GSE one, occurred from all the cryoprotected formulations. Finally, sucrose increased the physical stability of SLNs better than Me-ß-CD, whereas RPMI 2650 cell viability was unaffected by SLN-sucrose and slightly reduced by SLN-Me-ß-CD. (4) Conclusions: Sucrose can be considered a promising excipient, eliciting cryoprotection of the investigated SLNs, leading to a powder nasal pharmaceutical dosage form suitable to be handled by PD patients.

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 30 days. 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.

Inactivation Mechanism and Efficacy of Grape Seed Extract for Human Norovirus Surrogate.

Proper disinfection of harvested food and water is critical to minimize infectious disease. Grape seed extract (GSE), a commonly used health supplement, is a mixture of plant-derived polyphenols. Polyphenols possess antimicrobial and antifungal properties, but antiviral effects are not well-known. Here we show that GSE outperformed chemical disinfectants (e.g., free chlorine and peracetic acids) in inactivating Tulane virus, a human norovirus surrogate. GSE induced virus aggregation, a process that correlated with a decrease in virus titers. This aggregation and disinfection were not reversible. Molecular docking simulations indicate that polyphenols potentially formed hydrogen bonds and strong hydrophobic interactions with specific residues in viral capsid proteins. Together, these data suggest that polyphenols physically associate with viral capsid proteins to aggregate viruses as a means to inhibit virus entry into the host cell. Plant-based polyphenols like GSE are an attractive alternative to chemical disinfectants to remove infectious viruses from water or food. IMPORTANCE Human noroviruses are major food- and waterborne pathogens, causing approximately 20% of all cases of acute gastroenteritis cases in developing and developed countries. Proper sanitation or disinfection are critical strategies to minimize human norovirus-caused disease until a reliable vaccine is created. Grape seed extract (GSE) is a mixture of plant-derived polyphenols used as a health supplement. Polyphenols are known for antimicrobial, antifungal, and antibiofilm activities, but antiviral effects are not well-known. In studies presented here, plant-derived polyphenols outperformed chemical disinfectants (i.e., free chlorine and peracetic acids) in inactivating Tulane virus, a human norovirus surrogate. Based on data from molecular assays and molecular docking simulations, the current model is that the polyphenols in GSE bind to the Tulane virus capsid, an event that triggers virion aggregation. It is thought that this aggregation prevents Tulane virus from entering host cells.

The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis.

The objective of this systematic review and meta-analysis of controlled trials was to assess the long-term effect of grape seed extract (GSE) supplementation on flow-mediated dilation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in adults. Web of Science, Scopus, Medline, Cochrane Library, and Google Scholar were searched up to May 24, 2021. Nineteen trials were included in this study. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a random-effects model. GSE supplementation significantly reduced DBP (WMD: -2.20 mmHg, 95% CI: -3.79 to -0.60, I2 = 88.8%) and HR (WMD: -1.25 bpm, 95% CI: -2.32 to -0.19, I2 = 59.5%) but had no significant effects on FMD (WMD: 1.02%, 95% CI: -0.62 to 2.66, I2 = 92.0%) and SBP (WMD: -3.55 mmHg, 95% CI: -7.59 to 0.49, I2 = 97.4%). Subgroup analysis revealed that the dose and duration of GSE administration and the characteristics of study participants could be sources of between-study heterogeneity. Significant non-linear relationships were found between DBP and the duration of GSE supplementation (P = 0.044) and its dose (P = 0.007). In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.

Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial.

Grapes are polyphenol-rich, and grape juice intake has shown cognitive benefits in middle-aged females and older adults with mild cognitive impairment. Extracts obtained from grape seeds have similarly been associated with cognitive benefits in older adults. The aim of this research was to investigate whether a highly purified grape seed-derived polyphenol extract was associated with cognitive benefits in healthy young adults following a single acute dose, and chronically following repeated daily dosage over 12 weeks. Following an acute-on-chronic, parallel groups, randomised, double-blind, placebo-controlled design, sixty adults aged 18-30 consumed either a 400 mg grape seed polyphenol extract (GSPE, n = 30) or a placebo (n = 30). Cognitive function was assessed acutely at baseline and 2, 4 and 6 h post consumption, and chronically at 6 and 12 twelve weeks with a computerised battery of multiple cognitive tests. Mood was assessed with the Positive and Negative Affect Schedule. Linear marginal model analysis with baseline included as a covariate did not reveal a consistent pattern of cognitive benefits following the GSPE relative to the placebo either acutely or chronically when considering all outcome measures. GSPE was associated with some improvements in reaction time (acutely) and psychomotor skill (chronically), however the placebo was also associated with some benefits to reaction time and memory. Therefore, a 400 mg GSPE did not consistently improve cognitive function in healthy young adults. These findings suggest that younger, healthy populations are perhaps less sensitive to polyphenol extract doses <400mg relative to older, or cognitively compromised populations.

5-HT3/7 and GABAB receptors mediate inhibition of trigeminal nociception by dietary supplementation of grape seed extract.

Background: Temporomandibular joint disorder is a prevalent orofacial pain condition involving sensitization and activation of trigeminal nociceptive neurons. Dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) was found to inhibit trigeminal nociception in a chronic TMD model. In this study, the cellular mechanisms by which GSE inhibits sustained trigeminal nociception in male and female Sprague Dawley rats were investigated.Methods: Some animals were supplemented with 0.5% GSE dissolved in their water one week prior to neck muscle inflammation induced by injection of complete Freund's adjuvant into the trapezius. To investigate the mechanism of GSE, some animals were injected intracisternally with antagonists of 5-HT3, 5-HT7, GABAA, or GABAB, receptor prior to jaw opening.Results: In males and females, trapezius inflammation prior to jaw opening resulted in sustained mechanical hypersensitivity of trigeminal nociceptors that was significantly inhibited by GSE. Further, GSE beginning 14 days post jaw opening also inhibited trigeminal nociception. Intracisternal injection of antagonists of the 5-HT3/7 and GABAB, but not GABAA receptors reduced the anti-nocifensive effect of GSE in both sexes. Neuronal expression of GABAB protein and mRNA in the spinal cord and trigeminal ganglion were detected.Conclusions: The inhibitory effect of GSE is mediated via activation of 5-HT3/7 receptors and GABAB to enhance central descending inhibitory pain pathways and suppress ongoing trigeminal nociception. Further, our findings support the use of GSE as a dietary supplement in the management of pain associated with TMD and other orofacial pain conditions involving central sensitization and dysfunction of descending pain modulation.

Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. Can this extract improve learning and memory in aged animals?

BACKGROUND: During the elderly, hippocampal neurogenesis and synaptogenesis reduce and dark neurons (DNs) increase, leading to cognitive impairment. It is believed that natural products can protect the neural cells and system by protecting from damages or promoting regeneration. Therefore, the effects of grape seed extract (GSE) on the hippocampus of aged mice were investigated in this study. METHODS: twelve old mice were divided into two groups of control and GSE. Animals in the GSE group received 300 mg/kg of GSE for eight weeks via gavage. At the end of treatment, cognition performance was evaluated by Morris water maze (MWM) and passive avoidance tests. Hippocampal neurogenesis, synaptogenesis and DNs production were evaluated with immunohistochemistry and histological evaluations on 5-micron coronal tissue sections. RESULTS: The hippocampal mean number of double cortin positive cells (DCX+) per unit area, as well as synaptophysin expression in the GSE group, were significantly higher than the control group (p < 0.01). The frequency of DNs in the GSE group was lower than the control group (p < 0.05). Behavioral tests showed that GSE improves memory and learning performance. CONCLUSION: Consuming GSE in the elderly can potentially alleviate the age-related reduction of hippocampal neurogenesis and synaptogenesis. It is also able to decrease hippocampal DNs production and increase memory and learning.

Phenol Derivatives Obtained from Grape Seed Extract Show Virucidal Activity against Murine Norovirus.

Human noroviruses are the most common pathogens known to cause acute gastroenteritis, a condition that can lead to severe illness among immunocompromised individuals such as organ transplant recipients and the elderly. To date, no safe and effective vaccines or therapeutic agents have been approved for treating norovirus infections. Therefore, we aimed to demonstrate the virucidal activity of grape seed extract (GSE), which contains >83% proanthocyanidins, against murine norovirus (MNV), a surrogate for human norovirus. GSE showed virucidal activity against MNV in a dose- and time-dependent manner. Atomic force microscopic analysis showed viral particle aggregates after treatment of MNV with GSE. MNV treated with 50 µg/mL of GSE for 10 min resulted in the absence of pathogenicity in an animal model of infection, indicating that GSE has irreversible virucidal activity against MNV particles. Thus, GSE may aid in the development of treatments for norovirus infections.

Improved Analysis of Isomeric Polyphenol Dimers Using the 4th Dimension of Trapped Ion Mobility Spectrometry-Mass Spectrometry.

Dehydrodicatechins resulting from (epi)catechin oxidation have been investigated in different foods and natural products, but they still offer some analytical challenges. The purpose of this research is to develop a method using ultra-high performance liquid chromatography coupled with trapped ion mobility spectrometry and tandem mass spectrometry (UHPLC-ESI-TIMS-QTOF-MS/MS) to improve the characterization of dehydrodicatechins from model solutions (oxidation dimers of (+)-catechin and/or (-)-epicatechin). Approximately 30 dehydrodicatechins were detected in the model solutions, including dehydrodicatechins B with ß and ε-interflavanic configurations and dehydrodicatechins A with γ-configuration. A total of 11 dehydrodicatechins B, based on (-)-epicatechin, (+)-catechin, or both, were tentatively identified in a grape seed extract. All of them were of ß-configuration, except for one compound that was of ε-configuration. TIMS allowed the mobility separation of chromatographically coeluted isomers including dehydrodicatechins and procyanidins with similar MS/MS fragmentation patterns that would hardly be distinguished by LC-MS/MS alone, which demonstrates the superiority of TIMS added to LC-MS/MS for these kinds of compounds. To the best of our knowledge, this is the first time that ion mobility spectrometry (IMS) was applied to the analysis of dehydrodicatechins. This method can be adapted for other natural products.

Assessment of the Remineralizing Efficacy of Grape Seed Extract vs Sodium Fluoride on Surface and Subsurface Enamel Lesions: An In Vitro Study.

AIM: The aim of this study was to evaluate the efficacy of grape seed extract (GSE) on remineralization of surface and subsurface enamel lesions compared to that of sodium fluoride (NaF). MATERIALS AND METHODS: A total of 20 intact bovine incisor crowns were separated from their roots and immersed in a demineralizing solution for 96 hours at 37°C to create artificial enamel lesions. The specimens were randomly divided into two groups (n = 10): 6.5% GSE solution and 1000 ppm NaF solution. The specimens were subjected to six daily pH cycles for 8 days. The microhardness test was carried out at three different stages: baseline, after artificial caries formation, and after pH cycling. Raman spectroscopy was used to evaluate the depth of enamel remineralization. Surface morphology and elemental analysis were assessed using a scanning electron microscope (SEM) and an energy dispersive X-ray (EDX) spectroscope, respectively. Statistical analysis was performed using SPSS 22.0 at a significance level of p ≤ 0.05. RESULTS: There was a significant increase in the mean values of enamel surface microhardness after pH cycles in the two groups compared to after artificial caries formation, but there was no significant difference between both groups. The B-type carbonate/phosphate (Ca/P) ratio at 10 and 40 µm depth revealed no significant difference between the two groups. Scanning electron microscope micrograph revealed occlusion of porosities and particle precipitation on the enamel surface of the two groups, while EDX results for the Ca/P ratio of the GSE and NaF groups were 1.59 and 1.60, respectively. CONCLUSION: Grape seed extract and NaF are equally effective in remineralizing surface and subsurface artificial enamel lesions. CLINICAL SIGNIFICANCE: Grape seed extract can be considered a promising herbal material and a safe alternative to traditional NaF for the noninvasive treatment of enamel lesions.