Search Results (72)

This study employed UPLC-MS/MS to determine the contents of major polyphenolic compounds and proanthocyanidins (PCs) in Kyoho grape seeds, optimized the extraction method and conditions for PCs using response surface methodology (RSM), and further evaluated the scavenging activities of PCs against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (•OH) radicals as well as their effects on growth, immunity, and oxidative stress in mice. Three hundred and sixty 3-week-old male mice (42.28 ± 0.31 g) were assigned to a single factor complete randomized trial design and fed with six different diets including 0 mg/kg vitamin E(VE) + 0 mg/kg PCs, 100 mg/kg VE, 25 mg/kg PCs + 75 mg/kg VE, 50 mg/kg PCs + 50 mg/kg VE, 75 mg/kg PCs + 25 mg/kg VE and 100 mg/kg PCs, respectively. The results demonstrated that PCs were identified as the predominant phenolic compounds, accounting for 29.6% of total phenolic substances in Kyoho grape seeds. Additionally, the ultrasound-assisted extraction method was superior to the shaker-assisted and low-temperature infiltration extraction methods, with optimal conditions of 60% ethanol concentration, material-to-liquid ratio of 1:20 g/mL, temperature of 30 °C, and extraction time of 50 min. Scanning electron microscopy (SEM) revealed that ultrasound treatment effectively disrupted the seed surface structure, facilitating PC release. In vitro, PCs exhibited significantly stronger DPPH and hydroxyl radical (•OH) scavenging activities than vitamin C (VC), Trolox, and gallic acid. Compared with the control group, mice fed diets containing PCs and VE showed higher superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-PX) activity, and total antioxidant capacity (TAOC), Catalase (CAT), GPX and inflammation factor 10 (IL-10) genes levels in the serum and liver (p < 0.05), whereas the levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as the mRNA expression of IL-1β and TNF-α, showed the opposite trend (p < 0.05). In conclusion, the antioxidant capacity of PCs was stronger than that of VC and VE. The addition of PCs improved the antioxidant activity and immune function of mice. Full article

Background: Chronic inflammatory enteropathies (CIEs) in dogs are multifactorial disorders characterized by mucosal immune dysregulation, compromised epithelial barrier function, and increased exposure to microbial components such as lipopolysaccharide (LPS). The resulting oxidative stress and inflammation contribute to local and systemic pathology. Objective: This study aimed to evaluate the immunomodulatory and antioxidant effects of three naturally occurring flavonoids—quercetin, luteolin, and grape seed extract oligomeric proanthocyanidins (GSOPs)—in LPS-stimulated canine duodenal explants. Methods: Duodenal tissue samples were cultured in vitro and challenged with LPS derived from Escherichia coli and Salmonella enterica. Explants were co-incubated with flavonoid compounds, and endpoints included evaluation of histological architecture, inflammatory cytokine production, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Results: All three flavonoids attenuated LPS-induced mucosal inflammation and ROS production to varying degrees. In addition, GSOPs significantly reduced RNS levels under both basal and LPS-stimulated conditions. Quercetin and luteolin demonstrated pronounced downregulation of TNF-α, while both compounds also reduced IL-6 concentrations under non-stimulated conditions. These effects support the hypothesis that flavonoids can mitigate both inflammatory and oxidative responses under conditions relevant to CIE. Conclusion: Quercetin, luteolin, and GSOPs show promising in vitro efficacy in modulating key mechanisms implicated in canine CIE. Their multimodal actions highlight their potential as adjunctive nutraceuticals for the management of CIE in dogs. However, further in vivo validation is warranted. Full article

Background/Objectives: Recent research highlights Vitis vinifera seeds as a rich source of bioactive proanthocyanidins (PACs) with antioxidant and immunomodulatory effects. Poorly absorbed PACs are metabolized by gut microbiota into active phenolic metabolites. This pilot study in ulcerative colitis patients assessed grape seed extract effects on microbiota, zonulin-related permeability, and quality of life. Methods: This prospective pilot study, conducted at the University Hospital of Padua, evaluated the effects of an eight-week treatment with proanthocyanidins (ECOVITIS^®) on gut microbiota, intestinal permeability (zonulin), and well-being in patients with ulcerative colitis in remission (IBDQ). Fecal and serum samples were collected at T0 and T1. Microbiota analysis was performed through 16S rRNA gene sequencing (QIIME2), zonulin was quantified using an ELISA kit for pre-haptoglobin gene2 (pre-HP2), and HP1/HP2 genotyping was conducted by quantitative PCR. Statistical analyses (Wilcoxon, ALDEx2, PERMANOVA) assessed microbial diversity and taxonomic changes between pre- and post-treatment samples. Results: Twenty-five ulcerative colitis patients completed the study. IBDQ scores significantly improved after treatment (mean Δ = +11.2, p < 0.001), especially in the 11 best IBDQ responders (Δ = +24.2, p < 0.001). Microbiota analysis showed increased Lachnospiraceae and Sutterellaceae in responders, while overall diversity remained unchanged. Zonulin levels were unaffected. Conclusions: PAC treatment improved quality of life in ulcerative colitis patients, as shown by increased IBDQ scores. Serum zonulin levels remained unchanged. Microbiota analysis revealed enrichment of Lachnospiraceae and Sutterellaceae families, suggesting beneficial modulation. Limitations include lack of metabolic assessment and a control group, and caution is needed in interpreting zonulin measurements. Full article

Backgrounds and aim: Protective effects of natural compounds have been suggested in the prevention and treatment of radiation-induced mucositis or bacterial infections. In this study, the protective effects of proanthocyanidin-rich grape seed extract (GSE) on bacterial Lipopolysaccharide (LPS) and radiation-induced epithelial barrier damage and Reactive Oxygen Species (ROS) production were investigated in an in vitro model. Methods: Human intestinal epithelial cells Caco-2, previously treated with LPS, GSE, or LPS + GSE, were irradiated with 10 Gy divided into five daily treatments. Epithelial barrier integrity and ROS production were measured before and after each treatment. Results: Irradiation, at different doses, significantly increased intestinal permeability and ROS production; pretreatment with GSE was able to significantly prevent the increased intestinal permeability (4.63 ± 0.76 vs. 15.04 ± 1.5; p < 0.05) and ROS production (12.9 ± 1.08 vs. 1048 ± 0.5; p < 0.0001) induced by irradiation treatment. When the cells were pretreated with LPS, the same results were observed: GSE cotreatment was responsible for preventing permeability alterations (5.36 ± 0.16 vs. 49.26 ± 0.82; p < 0.05) and ROS production (349 ± 1 vs. 7897.67 ± 1.53; p < 0.0001) induced by LPS exposure when added to the irradiation treatment. Conclusions: The results of the present investigation demonstrated, in an in vitro model, that GSE prevents the damage to intestinal permeability and the production of ROS that are induced by LPS and ionizing radiation, suggesting a potential protective effect of this extract on the intestinal mucosa during irradiation treatment. Full article

Three experiments were conducted to investigate the effects of grape seed proanthocyanidin extract (GSPE) on the growth performance of weaned Hyla rabbits and explore its protective effects against oxidative stress in the liver and intestine by establishing a hydrogen peroxide (H₂O₂)-induced oxidative stress model. In Exp.1, ninety-six weaned rabbits were used to evaluate the effects of dietary GSPE level on growth performance, and the results showed that a 400 mg/kg GSPE addition increased the feed conversion ratio and liver coefficient and promoted cholesterol metabolism. Exp.2 was conducted to explore the H₂O₂ concentration required to establish an oxidative stress model, indicating that the model could be established by an intraperitoneal injection of 10% H₂O₂ at a dosage of 1 mL/kg body weight. In Exp.3, seventy-two weaned rabbits were used to investigate the protective effects against H₂O₂-induced oxidative stress in the liver and intestine. Our findings showed that 400 mg/kg GSPE supplementation could alleviate the adverse effects of H₂O₂ injection on the antioxidant capacity in the liver and intestine as well as liver morphology. Therefore, an addition of 400 mg/kg GSPE could improve growth performance and alleviate H₂O₂-induced adverse effects on the liver and small intestine by enhancing the antioxidative capacity in weaned Hyla rabbits. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse). Methods: These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed. Results: Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates. Conclusions: These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food. Full article

Few investigations have been conducted to evaluate pressurized liquid extraction (PLE) technology as a sustainable method for the recovery of phenolic compounds of grape seed by-products. In this study, PLE combined with an experimental design was evaluated for optimizing the sustainable extraction of phenolic compounds from grape seed by-products. The solvent ethanol content (X1, 0–100%), temperature (X2, 20–100 °C) and time (X3, 1–11 min) were studied as independent experimental factors. Yield, TPC, antioxidant activity and phenolic composition were analyzed as optimized dependent variables. Two optimal extraction conditions at different temperatures (20 °C and 100 °C) were found, but thermal degradations at 100 °C allowed for selecting the optimal condition as 75% ethanol, 11 min and 20 °C. The optimal extracts showed high phenolic content (TPC = 350.80 ± 3.97 mg GAE/g extract) and antioxidant activity (ABTS, 9.31 ± 0.33 mmol Trolox/g extract), mainly composed of polymeric and mono-oligomeric flavan-3-ols. The digestion process reduced the TPC and antioxidant activity due to the low bioaccessibility of the flavan-3-ols, mainly as catechin, epicatechin and polymeric proanthocyanidin losses during the digestion process. However, increases in the antioxidant activity of the basolateral side (DDPH, 0.061 ± 0.000 mmol Trolox/g extract) were determined after in vitro transepithelial transport, which is a consequence of bioavailable catechin and epicatechin and reduced amounts of dimer B₂, dimer B₁, epicatechin gallate and gallic acid. Consequently, PLE combined with hydroalcoholic solvents at a low temperature resulted in a valuable methodology to obtain sustainable extracts from grape seed by-products (contributing to the circular economy), containing bioavailable phenolic compounds, which are able to increase the antioxidant status. Full article

Background: Grape seed extract (GSE) from Vitis vinifera L. is rich in polyphenols and oligomeric proanthocyanidin complexes (OPCs), and it has shown potential benefits in managing low mood and cognitive function. In this study, we investigated the potential bioactivities of Enovita^®, a standardized GSE extract (GSEe herein) rich in OPCs, in key mechanistic pathways related to low mood conditions and cognitive function. Methods: In vitro assays were conducted to assess GSEe’s inhibitory effects on γ-aminobutyric acid transaminase (GABA-T) and monoamine oxidase A (MAO-A), its binding affinity to the GABA site of GABA-A receptors, and its effects on acetylcholinesterase (AChE). Its neuroprotective effects on human SH-SY5Y neuroblastoma cells under oxidative stress (induced by H₂O₂) were assessed using MTT and LDH release assays. Its antioxidant activities were evaluated using DPPH, ABTS, FRAP, ORAC, HORAC, total phenolic content, and TAS assays. Its cytotoxicity was also evaluated. Results: GSEe showed significant GABA-T inhibitory activity. It also exhibited MAO-A and AChE inhibition, along with moderate binding affinity to the GABA-A receptor. In neuroprotective assays, GSEe provided significant protection to SH-SY5Y cells against oxidative stress. GSEe demonstrated robust antioxidant activity in all assays, including scavenging of DPPH and ABTS radicals, high ferric-reducing power, high polyphenolic contents, and a substantial total antioxidant capacity. Conclusions: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function. Full article

This study investigated the influence of photoperiod (day length) on the efficacy of grape seed proanthocyanidin extract (GSPE) in mitigating metabolic disorders in obese rats fed a cafeteria diet. Rats were exposed to standard (L12), long (L18), or short (L6) photoperiods and treated with GSPE or vehicle. In the standard photoperiod, GSPE reduced body weight gain (50.5%), total cholesterol (37%), and triglycerides (34.8%), while increasing the expression of hepatic metabolic genes. In the long photoperiod, GSPE tended to decrease body weight gain, increased testosterone levels (68.3%), decreased liver weight (12.4%), and decreased reverse serum amino acids. In the short photoperiod, GSPE reduced glycemia (~10%) and lowered triglyceride levels (38.5%), with effects modified by diet. The standard photoperiod showed the greatest efficacy against metabolic syndrome-associated diseases. The study showed how day length affects GSPE’s benefits and underscores considering biological rhythms in metabolic disease therapies. Full article

The purpose of the present study was to prepare pectin hydrogels with immobilized Lemna minor callus cells and to identify the effect of cell immobilization on the textural, rheological, and swelling properties; loading; and releasing of grape seed extract (GSE) from the hydrogels. Hardness, adhesiveness, elasticity, the strength of linkage, and complex viscosity decreased with increasing cell content in the hydrogels based on pectin with a degree of methyl esterification (DM) of 5.7% (TVC) and during incubation in gastrointestinal fluids. An increase in the rheological properties and fragility of pectin/callus hydrogels based on pectin with a DM of 33.0% (CP) was observed at a cell content of 0.4 g/mL. TVC-based pectin/callus beads increased their swelling in gastrointestinal fluids as cell content increased. TVC-based beads released GSE very slowly into simulated gastric and intestinal fluids, indicating controlled release. The GSE release rate in colonic fluid decreased with increasing cell content, which was associated with the accumulation of GSE in cells. CP-based beads released GSE completely in the intestinal fluid due to weak textural characteristics and rapid degradation within 10 min. Pectin/callus hydrogels have the ability to preserve GSE for a long time and may have great potential for the development of proanthocyanidin delivery systems due to their novel beneficial physicochemical and textural properties. Full article

Disruptions of the light/dark cycle and unhealthy diets can promote misalignment of biological rhythms and metabolic alterations, ultimately leading to an oxidative stress condition. Grape seed proanthocyanidin extract (GSPE), which possesses antioxidant properties, has demonstrated its beneficial effects in metabolic-associated diseases and its potential role in modulating circadian disruptions. Therefore, this study aimed to assess the impact of GSPE administration on the liver oxidant system of healthy and diet-induced obese rats undergoing a sudden photoperiod shift. To this end, forty-eight photoperiod-sensitive Fischer 344/IcoCrl rats were fed either a standard (STD) or a cafeteria diet (CAF) for 6 weeks. A week before euthanizing, rats were abruptly transferred from a standard photoperiod of 12 h of light/day (L12) to either a short (6 h light/day, L6) or a long photoperiod (18 h light/day, L18) while receiving a daily oral dose of vehicle (VH) or GSPE (25 mg/kg). Alterations in body weight gain, serum and liver biochemical parameters, antioxidant gene and protein expression, and antioxidant metabolites were observed. Interestingly, GSPE partially ameliorated these effects by reducing the oxidative stress status in L6 through an increase in GPx1 expression and in hepatic antioxidant metabolites and in L18 by increasing the NRF2/KEAP1/ARE pathway, thereby showing potential in the treatment of circadian-related disorders by increasing the hepatic antioxidant response in a photoperiod-dependent manner. Full article

(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-β-cyclodextrin (Me-β-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-β-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-β-CD, whereas RPMI 2650 cell viability was unaffected by SLN-sucrose and slightly reduced by SLN-Me-β-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. Full article

With a reduced supply and increased price of white fish meal (WFM), the exploration of a practical strategy to replace WFM is urgent for sustainable eel culture. A 70-day feeding trial was conducted to evaluate the effects of replacing WFM with low-quality brown fish meal (LQBFM) with compound additives (CAs) on the growth performance and intestinal health of juvenile American eels (Anguilla rostrata). The 300 fish (11.02 ± 0.02 g/fish) were randomly distributed in triplicate to four groups (control group, LQBFM20+CAs group, LQBFM30+CAs group and LQBFM40+CAs group). They were fed the diets with LQBFM replacing WFM at 0, 20%, 30% and 40%, respectively. The CAs were a mixture of Macleaya cordata extract, grape seed proanthocyanidins and compound acidifiers; its level in the diets of the trial groups was 0.50%. No significant differences were found in the growth performance between the control and LQBFM20+CAs groups (p > 0.05), whereas those values were significantly decreased in LQBFM30+CAs and LQBFM40+CAs groups (p < 0.05). Compared to the control group, the activity of glutamic-pyruvic transaminase was significantly increased in LQBFM30+CAs and LQBFM40+CAs groups, while lysozyme activity and complement 3 level were significantly decreased in those two groups (p < 0.05). There were decreased antioxidant potential and intestinal morphological indexes in the LQBFM30+CAs and LQBFM40+CAs groups, and no significant differences in those parameters were observed between the control group and LQBFM20+CAs group (p > 0.05). The intestinal microbiota at the phylum level or genus level was beneficially regulated in the LQBFM20+CAs group; similar results were not shown in the LQBFM40+CAs group. In conclusion, with 0.50% CA supplementation in the diet, LQBFM could replace 20% of WFM without detrimental effects on the growth and intestinal health of juvenile American eels and replacing 30% and 40%WFM with LQBFM might exert negative effects on this fish species. Full article

Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes. Full article

Grapes, especially those of the red varieties, have a high content of polyphenolic compounds. After the removal of the juice during the winemaking process, the grape marc (peels and seeds) remains as waste, making it a promising source for the isolation of polyphenols. The separation, recovery, and enrichment of samples of phenolic compounds offers the possibility of their subsequent utilization in the food, pharmaceutical, and cosmetics industries. In this paper, results are presented on both laboratory and pilot scales, including the effect of basic extraction parameters such as the solvent (water, ethanol, acetone, polyethylene glycol, ethyl acetate, and their respective 50% aqueous solutions), the solid/liquid ratio, the extraction time, and the temperature. The enrichment of the extracts in phenolic compounds was performed with the help of a series of membrane processes and rotary evaporation. The experiments showed the presence of almost all known compounds reported in the literature with pro-anthocyanidins (dimers-trimers) and flavan-3-ols together with various metabolites accompanied by a significant reduction in the values of total organic load. Full article