Grape Seed Proanthocyanidin Extract Research Articles

Evaluating the Renal and Splenic Protective Effects of Grape Seed Proanthocyanidin Extract in Diethylnitrosamine-Induced Male Sprague Dawle

Evaluating the Renal and Splenic Protective Effects of Grape Seed Proanthocyanidin Extract in Diethylnitrosamine-Induced Male Sprague Dawle

Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation through modulation of cecal microbiota and enhanced butyric acid production.

The conversion of fast-twitch fibers into slow-twitch fibers within skeletal muscle plays a crucial role in improving physical stamina and safeguarding against metabolic disorders in individuals. Grape seed proanthocyanidin extract (GSPE) possesses numerous pharmacological and health advantages, effectively inhibiting the onset of chronic illnesses. However, there is a lack of research on the specific mechanisms by which GSPE influences muscle physiology and gut microbiota. This study aims to investigate the role of gut microbiota and their metabolites in GSPE regulation of skeletal muscle fiber type conversion. In this experiment, 54 male BALB/c mice were randomly divided into three groups: basal diet, basal diet supplemented with GSPE, and basal diet supplemented with GSPE and antibiotics. During the feeding period, glucose tolerance and forced swimming tests were performed. After euthanasia, samples of muscle and feces were collected for analysis. The results showed that GSPE increased the muscle mass and anti-fatigue capacity of the mice, as well as the expression of slow-twitch fibers. However, the beneficial effects of GSPE on skeletal muscle fibers disappeared after adding antibiotics to eliminate intestinal microorganisms, suggesting that GSPE may play a role by regulating intestinal microbial structure. In addition, GSPE increased the relative abundance of Blautia, Muribaculaceae, and Enterorhabdus, as well as butyrate production. Importantly, these gut microbes exhibited a significant positive correlation with the expression of slow-twitch muscle fibers. In conclusion, supplementation with GSPE can increase the levels of slow-twitch fibers by modulating the gut microbiota, consequently prolonging the duration of exercise before exhaustion. PRACTICAL APPLICATION: This research suggests that grape seed proanthocyanidin extract (GSPE) has potential applications in improving physical stamina and preventing metabolic disorders. By influencing the gut microbiota and increasing butyric acid production, GSPE contributes to the conversion of fast-twitch muscle fibers into slow-twitch fibers, thereby enhancing anti-fatigue capacity and exercise endurance. While further studies are needed, incorporating GSPE into dietary supplements or functional foods could support individuals seeking to optimize their exercise performance and overall metabolic health.

Grape Seed Proanthocyanidins Protect Pancreatic β Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.

Pancreatic β cell damage is the primary contributor to type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains nebulous. This study explored the role of ferroptosis in pancreatic β cell damage and the protective effects of grape seed proanthocyanidin extract (GSPE). In T2DM model rats, the blood glucose, water intake, urine volume, HbA1c, and homeostasis model assessment-insulin resistance were significantly increased, while the body weight and the insulin level were significantly decreased, indicating the successful establishment of the T2DM model. MIN6 mouse insulinoma β cells were cultured in high glucose and sodium palmitate conditions to obtain a glycolipid damage model, which was administered with GSPE, ferrostatin-1 (Fer-1), or nuclear factor erythroid 2-related factor 2 (Nrf2) small interfering (si) RNA. GSPE and Fer-1 treatment significantly improved pancreatic β-cell dysfunction and protected against cell death. Both treatments increased the superoxide dismutase and glutathione activity, reduced the malondialdehyde and reactive oxygen species levels, and improved iron metabolism. Furthermore, the treatments reversed the expression of ferroptosis markers cysteine/glutamate transporter (XCT) and glutathione peroxidase 4 (GPX4) caused by glycolipid toxicity. GSPE treatments activated the expression of Nrf2 and related proteins. These effects were reversed when co-transfected with si-Nrf2. GSPE inhibits ferroptosis by activating the Nrf2 signaling pathway, thus reducing β-cell damage and dysfunction in T2DM. Therefore, GSPE is a potential treatment strategy against T2DM.

Dietary short-term supplementation of grape seed proanthocyanidin extract improves pork quality and promotes skeletal muscle fiber type conversion in finishing pigs

Plant extracts are commonly used as feed additives to improve pork quality. However, due to their high cost, shortening the duration of supplement use can help reduce production costs. In this study, we aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on meat quality and muscle fiber characteristics of finishing pigs during the late stage of fattening, which was 30 days in our experimental design. The results indicated that short-term dietary supplementation of GSPE significantly reduced backfat thickness, but increased loin eye area and improved meat color and tenderness. Moreover, GSPE increased slow myosin heavy chain (MyHC) expression and malate dehydrogenase (MDH) activity, while decreasing fast MyHC expression and lactate dehydrogenase (LDH) activity in the Longissimus thoracis (LT) muscle. Additionally, GSPE increased the expression of Sirt1 and PGC-1α proteins in the LT muscle of finishing pigs and upregulated AMP-activated protein kinase α 1 (AMPKα1), AMPKα2, nuclear respiratory factor 1 (NRF1), and calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) mRNA expression levels. These findings suggest that even during the late stage of fattening, GSPE treatment can regulate skeletal muscle fiber type transformation through the AMPK signaling pathway, thereby affecting the muscle quality of finishing pigs. Therefore, by incorporating GSPE into the diet of pigs during the late stage of fattening, producers can enhance pork quality while reducing production costs.

Grape seed proanthocyanidin extract alleviates inflammation in experimental colitis mice by inhibiting NF-κB signaling pathway.

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.

Immunomodulatory effects of aflatoxin B1 (AFB1) and the use of natural products to ameliorate its immunotoxic effects: A review

Aflatoxin B1 (AFB1), a potent mycotoxin, is known to be an immunotoxic agent that causes various immune system disorders. It can cause immunosuppression by direct toxic effect on the host or by its ability to interfere with the immune response and thereby lead to secondary infections. The immunomodulatory effects of AFB1 and its metabolites have been reported in many studies. Yet, the exact mechanisms responsible for these immunomodulatory effects are still obscure. This review summarizes the current findings on the interaction between AFB1 and the host immune system, while also highlighting other potential mechanisms involved in AFB1-induced immunosuppression. These potential mechanisms include modulation of cytokine production, production of inflammatory mediators and their receptors, activation of pro-inflammatory pathways, alteration in cell surface receptors involved in T cell activation and regulation of apoptosis. The review also discusses recent findings on natural products that have been found capable of inhibiting AFB1-induced immunosuppression in various animal models. With the latest exploration of natural products as a solution, the burden of aflatoxicosis in society is likely to subdue. Some of the promising natural products that have been highlighted to have ameliorative effects include grape seed proanthocyanidin extract (GSPE), bentonite clay, NovaSil Clay and Spirulina plantesis among others. Considering the seriousness of aflatoxicosis in the public domain and lack of effective management approaches, there is an urgent need for more research to understand AFB1-induced immunotoxicity and possible remedies.

Abrupt Photoperiod Changes Differentially Modulate Hepatic Antioxidant Response in Healthy and Obese Rats: Effects of Grape Seed Proanthocyanidin Extract (GSPE)

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.

Dietary grape seed proanthocyanidin extract improved the chemical composition, antioxidant capacity, myofiber growth and flesh quality of Nile tilapia muscle

The effects of dietary grape seed proanthocyanidin extract (GSPE) supplementation (0, 100, 200, and 400 mg/kg) on the stress response, antioxidant status, myofiber growth, and meat quality of Nile tilapia were investigated in present study. Dietary GSPE lowered serum stress-related parameters (cortisol, glucose, Na+, and lactate) and improved the total antioxidant capability with enhanced superoxide dismutase and catalase activities and reduced levels of reactive oxygen species. Meanwhile, myoglobin content, pH, color, tenderness, the water-holding capacity were improved. Dietary GSPE also increased the contents of delicious amino acids, flavor amino acids, and total amino acids, C18:3n-3 (ALA), C20:5n-3 (EPA), n-3 poly-unsaturated fatty acids, decreasing off-flavor compounds such as aldehydes and alcohols. Moreover, GSPE supplementation improved myofiber growth and muscle protein deposition likely via the activation of the IGFs/PI3K/Akt/TOR/S6K1/4E-BP1 pathway, contributing to the enhanced growth performance of Nile tilapia (Oreochromis niloticus). Together, GSPE is a promising natural food additive that enhances various important meat quality parameters of fish, and the optimal dietary GSPE requirement for maximum growth and muscle protein deposition was approximately 280 mg/kg.

Grape seed proanthocyanidin extract modulates cigarette smoke extract-induced epithelial cell apoptosis by inhibiting oxidative stress in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible, inflammatory lung disease characterized by airway inflammation and emphysema. Cigarette smoke-induced oxidative stress and apoptosis of alveolar epithelial cells (AECs) are key factors in COPD pathogenesis. We investigated the effects of grape seed proanthocyanidin extract (GSPE) on cigarette smoke extract (CSE)-induced AEC apoptosis, emphysema, and inflammation. We exposed mice to CSE and evaluated histological changes, reactive oxygen species production, proinflammatory cytokine expression, and apoptosis levels in the lungs and AECs. GSPE exerted protective effects against CSE-induced COPD. The levels of reactive oxygen species were by GSPE in vitro and in vivo. GSPE significantly decreased the levels of reactive oxygen species in vitro and in vivo and reduced the number of macrophages, neutrophils and levels of cytokines in the bronchoalveolar lavage fluid and AECs, ameliorating lung inflammation. GSPE ameliorated the CSE-induced COPD development by inhibiting oxidative stress-induced epithelial cell apoptosis.

Dietary grape seed proanthocyanidin extract supplementation improves antioxidant capacity and lipid metabolism in finishing pigs

Grape seed proanthocyanidin extract (GSPE) plays a significant role in body health, including improving antioxidant capacity and maintaining lipid metabolism stability. However, whether dietary GSPE supplementation can improve lipid metabolism in finishing pigs remains unclear. Here 18 castrated male Duroc × Landrace × Yorkshire finishing pigs were randomly divided into three groups with six replicates and one pig per replicate. Pigs were fed a basal diet (control), a basal diet supplemented with 100 mg/kg GSPE, or a basal diet supplemented with 200 mg/kg GSPE for 30 days. Antioxidant analysis showed that dietary 200 mg/kg GSPE supplementation increased glutathione, total antioxidant capacity and glutathione peroxidase levels, and reduced malondialdehyde levels in serum, muscle and liver. Dietary 200 mg/kg GSPE supplementation also upregulated the mRNA and protein levels of nuclear-related factor 2 (Nrf2). Lipid metabolism analysis showed that dietary GSPE supplementation increased serum high-density lipoprotein cholesterol levels and reduced serum triglyceride and total cholesterol levels. Besides, GPSE upregulated the mRNA expression of lipolysis- and fatty acid oxidation-related genes downregulated the mRNA expression of lipogenesis-related genes, and activated the AMPK signal in finishing pigs. Together, we provided evidence that dietary GSPE supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.

Proanthocyanidin and sodium butyrate synergistically modulate rat colon carcinogenesis by scavenging free radicals and regulating the COX-2 and APC pathways

BackgroundThe purpose of this study was to explore the effects of sodium butyrate (NaB), grape seed proanthocyanidin extract (GSPE), or their combination against dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation, which is a proxy for colon carcinogenesis in the rat colon.ResultsAfter inducing colon cancer, all treatments markedly decreased the overall numbers of ACF, with the NaB–GSPE combination eliciting the most pronounced reduction. All the treatments significantly inhibited cell proliferation as indicated by the lower percentages of Ki67-positive cells in the colonic mucosa. Also, caspase-3-immunolabeled cells were found to be significantly increased after all treatments, indicating more apoptotic activity in the initiated colonocytes. Further, the treatments significantly modulated the levels of antioxidant biomarkers, including malondialdehyde, superoxide dismutase, reduced glutathione, and total antioxidant capacity, suggesting a potently induced antioxidant activity, especially after the combination treatment. All treatments, especially the combination, dramatically downregulated the expression of COX-2 and APC, both of which are directly linked to colon cancer.ConclusionsNaB and GSPE exert potent anti-carcinogenic effects, both alone but more effectively in combination, in a rat colon cancer model. They could be important for colon cancer treatment and for adjuvant therapy in humans.

Rhythm and ROS: Hepatic Chronotherapeutic Features of Grape Seed Proanthocyanidin Extract Treatment in Cafeteria Diet-Fed Rats.

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.

Photoperiod-Dependent Effects of Grape-Seed Proanthocyanidins on Adipose Tissue Metabolic Markers in Healthy Rats.

Variations in photoperiod patterns drive metabolic adaptations in mammals, involving important changes in body weight and adiposity. Moreover, (poly)phenols can help heterotrophs adopt metabolic adaptations to face the upcoming environmental conditions. Particularly, proanthocyanidins from grape-seeds show photoperiod-dependent effects on different metabolic parameters. The present study aims to explore whether grape-seed proanthocyanidin extract (GSPE) consumption differently affects the expression of metabolic markers in WAT (subcutaneous and visceral depots) and BAT in a photoperiod-dependent manner. GSPE (25mgkg-1 day-1 ) is orally administrated for 4 weeks to healthy rats exposed to three photoperiods (L6, L12, and L18). In WAT, GSPE consumption significantly upregulates the expression of lipolytic genes in all photoperiods, being accompanied by increased serum concentrations of glycerol and corticosterone only under the L6 photoperiod. Moreover, adiponectin mRNA levels are significantly upregulated in response to GSPE regardless of the photoperiod, whereas Tnfα and Il6 expression are only downregulated in L6 and L18 photoperiods but not in L12. In BAT, GSPE upregulates Pgc1α expression in all groups, whereas the expression of Pparα is only increased in L18. The results indicate that GSPE modulates the expression of important metabolic markers of WAT and BAT in a photoperiod-dependent manner.

Effects of grape seed proanthocyanidin extract on side effects of high-dose methylprednisolone administration in male rats.

In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food + intraperitoneal injection of 60mg/kg MP on day 7; (3) GSPE, received standard food + 200mg/kg/day GSPE; and (4) MP + GSPE, received standard food + 200mg/kg/day of GSPE + intraperitoneal injection of 60mg/kg MP on day 7. All animals in the GSPE and GSPE + MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP + GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p < 0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p < 0.001), glucose (p < 0.01), alkaline phosphatase, and adrenocorticotropic hormone (p < 0.05). High-dose MP administration significantly reduced catalase (p < 0.001) and glutathione peroxidase (p < 0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p < 0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p < 0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP + GSPE (p < 0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.

GSPE attenuates CSE-induced lung inflammation and emphysema by regulating autophagy via the reactive oxygen species/TFEB signaling pathway.

Cigarette smoke can enhance reactive oxygen species (ROS) production in inflammatory and epithelial cells. Subsequently, ROS enhance autophagy-induced inflammation due to alveolar macrophages (AMs), the primary source of cytokines implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, we hypothesized that grape seed proanthocyanidin extract (GSPE), an effective antioxidant, could inhibit emphysema and airway inflammation by ameliorating cigarette smoke extract (CSE)-induced autophagy via suppressing oxidative stress in macrophages. We observed that GSPE significantly attenuated histological changes observed in CSE-induced emphysema and airway inflammation in the lungs of mice. Moreover, GSPE ameliorated lung inflammation by reducing the number of cells, macrophages, and neutrophils and the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels measured in bronchioloalveolar lavage fluid. ROS levels increased after CSE instillation and significantly decreased with in vitro GSPE treatment. GSPE decreased transcription factor EB (TFEB) oxidation by reducing ROS, inhibiting TFEB nuclear translocation. Furthermore, GSPE inhibited ROS-induced autophagy in RAW 264.7cells, bone marrow-derived macrophages, and AMs. Inhibiting autophagy through GSPE treatment diminishes CSE-induced lung inflammation by inhibiting the NLRP3 inflammasome. This study demonstrates that GSPE can ameliorate CSE-induced inflammation and emphysema via autophagy-induced NLRP3 inflammasome regulation through the ROS/TFEB signaling pathway in a COPD mouse model.

The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis.

Histone deacetylase inhibitor (HDACi) is a drug mainly used to treat hematological tumors and breast cancer, but its inhibitory effect on breast cancer falls short of expectations. Grape seed proanthocyanidin extract (GSPE) with abundant proanthocyanidins (PAs) has been explored for its inhibition of HDAC activity in vitro and in vivo. To enhance HDACi's effectiveness, we investigated the potential of PA to synergistically enhance HDACi chidamide (Chi), and determined the underlying mechanism. We evaluated the half-inhibitory concentration (IC50) of PA and Chi using the cell counting kit 8 (CCK8), and analyzed drugs' synergistic effect with fixed-ratio combination using the software Compusyn. Breast cancer cell's phenotypes, including short-term and long-term proliferation, migration, invasion, apoptosis, and reactive oxygen species (ROS) levels, were assessed via CCK8, clone-formation assay, wound-healing test, Transwell Matrigel invasion assay, and flow-cytometry. Protein-protein interaction analysis (PPI) and KEGG pathway analysis were used to determine the underlying mechanism of synergy. PA + Chi synergistically inhibited cell growth in T47D and MDA-MB-231 breast cancer cell lines. Short-term and long-term proliferation were significantly inhibited, while cell apoptosis was promoted. Ten signaling pathways were identified to account for the synergistic effect after RNA sequencing. Their synergism may be closely related to the steroid biosynthesis and extracellular matrix (ECM) receptor interaction pathways. PA + Chi can synergistically inhibit breast cancer cell growth and proliferation, and promote apoptosis. These effects may be related to steroid biosynthesis or the ECM receptor pathway.

Effects of grape seed proanthocyanidin extract on lipopolysaccharide translocation and trafficking from the gut to tissues

Diet-associated alterations of the intestinal barrier and gut microbiota promote intestinal lipopolysaccharide (LPS) translocation from the lumen to the lamina propria through different pathways, leading to an increase in LPS levels in the plasma known as metabolic endotoxemia. As a pharmacological dose of grape seed proanthocyanidin extract (GSPE) can reduce metabolic endotoxemia of obese rats, in the current study, we aimed to evaluate GSPE modulation of LPS translocation and the underlying mechanisms. We performed both an in vitro experiment with Caco-2 cells and an in vivo experiment with Wistar female rats fed a cafeteria (CAF) diet. GSPE was effective in regulating intestinal permeability through the modulation of receptor-mediated endocytosis pathway, as well as the gut microbiota interaction with the endocannabinoid system through epigenetic mechanisms. Our results confirm that GSPE can ameliorate intestinal dysfunction and metabolic endotoxemia caused by an excess of dietary lipids by modulating the endotoxin-translocation pathways.

GSPE Pre-Treatment Exerts Long-Lasting Preventive Effects against Aging-Induced Changes in the Colonic Enterohormone Profile of Female Rats.

The impact that healthy aging can have on society has raised great interest in understanding aging mechanisms. However, the effects this biological process may have on the gastrointestinal tract (GIT) have not yet been fully described. Results in relation to changes observed in the enteroendocrine system along the GIT are controversial. Grape seed proanthocyanidin extracts (GSPE) have been shown to protect against several pathologies associated with aging. Based on previous results, we hypothesized that a GSPE pre-treatment could prevent the aging processes that affect the enteroendocrine system. To test this hypothesis, we treated 21-month-old female rats with GSPE for 10 days. Eleven weeks after the treatment, we analyzed the effects of GSPE by comparing these aged animals with young animals. Aging induced a greater endocrine response to stimulation in the upper GIT segments (cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1)), a decrease in the mRNA abundance of GLP-1, peptide YY (PYY) and chromogranin A (ChgA) in the colon, and an increase in colonic butyrate. GSPE-treated rats were protected against a decrease in enterohormone expression in the colon. This effect is not directly related to the abundance of microbiome or short-chain fatty acids (SCFA) at this location. GSPE may therefore be effective in preventing a decrease in the colonic abundance of enterohormone expression induced by aging.

Protective effects of grape seed proanthocyanidins on podocytes against injury induced by glucolipotoxicity

Diabetic nephropathy (DN) is the most common cause of end-stage renal failure, oxidative damage and iron metabolism disorder are related to DN progression, but the exact pathogenesis remains unclear. Grape seed proanthocyanidins extract (GSPE) are one of the most widely distributed polyphenols with antioxidant properties. Here, we evaluate the mechanism by which GSPE alleviates podocyte damage induced by high glucose and palmitic acid (HG/PA). Podocytes were cultured in groups in normal environment; these were based on whether HG/PA and ML385 were present and the concentrations GSPE 10 mg/L, GSPE 25 mg/L, and GSPE 50 mg/. The flow cytometer, immunofluorescence staining, western blot, quantitative real time-PCR (qRT-PCR), kit methodand, and fluorescence microscope were used, respectively. After HG/PA intervention, the podocyte morphology was destroyed, the survival rate was reduced, the cell apoptosis was increased, and the fluorescence intensity of ROS detection was increased, iron metabolism was disordered. After adding ML385, increased oxidative damage to podocyte, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein and mRNA expression levels were significantly reduced. However, the application of different concentrations of GSPE can reverse these situations. Our findings indicate that GSPE regulates intracellular iron metabolism disorders and reduces oxidative damage of podocytes possibly through the activation of the Nrf2 signaling pathway.

Grape Seed Proanthocyanidins Inhibit Replication of the Dengue Virus by Targeting NF-kB and MAPK-Mediated Cyclooxygenase-2 Expression.

Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.