Grape Seed Procyanidin Extract Research Articles

Grape seed proanthocyanins protect fluoride-induced hepatotoxicity via the Nrf2 signaling pathway in male rats.

Fluoride is a necessary element for human health, but excessive fluoride intake is found toxic to the liver. Previous studies confirmed that Grape seed procyanidin extract (GSPE) protects against fluoride-induced hepatic injury. However, the mechanism underlying this protective effect remains obscure. To evaluate the protective effect of GSPE against fluoride-induced hepatic injury and explore the possible hepatoprotective role of the Nrf2 signaling pathway to find effective strategies for the treatment and prevention of fluoride-induced hepatotoxicity. This study aims to explore the mechanisms by which GSPE attenuates fluoride-induced hepatotoxicity through a rat drinking water poisoning model. Hepatic injury was determined by serum biochemical parameters, oxidative parameters, HE, and TUNEL analysis. The protein expression levels of apoptosis-related proteins like Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 and the nuclear factor, erythroid 2 like 2 (Nrf2) were analyzed by Western blot. Our results showed that GSPE administration reduced fluoride-induced elevated serum ALT and AST and enhanced the antioxidant capacity of the liver. In addition, GSPE mitigated fluoride-induced histopathological damage and reduced the liver cell apoptosis rate. Furthermore, GSPE significantly up-regulated the expression and nuclear translocation of the Nrf2 and decreased apoptosis-related proteins like Bax and caspase-3 in the hepatic. Taken together, GSPE exerts protective effects on the oxidative damage and apoptosis of fluoride-induced hepatic injury via the activation of the Nrf2 signaling pathway. This study provides a new perspective for the mechanism study and scientific prevention and treatment of liver injury induced by endemic fluorosis.

The effect of grape seed procyanidins extract on cognitive function in elderly people with mild cognitive impairment: A randomized, double-blind, placebo-controlled clinical trial

BackgroundProcyanidins have antioxidative properties that may protect against age-related brain oxidative stress. Previous studies indicated that procyanidin-rich foods could improve cognitive function and prevent neurodegenerative diseases. This study hypothesized that grape seed procyanidins extract (GSPE) would have a favorable effect on cognitive function in elderly people with mild cognitive impairment (MCI). MethodsA community-based, randomized, double-blind, placebo-controlled trial was conducted. Participants aged 60 years or older with MCI were randomly assigned into the GSPE group (n = 35, 320 mg/d) or placebo group (n = 36), and received capsules for 6 months. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The change in MoCA scores between groups were tested by the time ✕ treatment interaction in mixed-design ANOVA. ResultsAfter 6 months of intervention, the MoCA score was higher than the baseline both in the intervention group and placebo control group, while the there was no significant difference for mean change in MoCA score from baseline between the intervention group and the placebo group (2.35 ± 3.20 vs. 1.28 ± 2.93, P = 0.192). ConclusionsPresent study showed that 6-month supplementation with GSPE did not significantly improve cognitive function in subjects with MCI. Further investigations regarding the longer-term intervention effect of procyanidins extract on mild or moderate cognitive disorders are needed.

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer — The role of MiR-663a and FHIT

AimsGrape seed procyanidin extract (GSE), and milk thistle silymarin extract (MTE) contain structurally distinct polyphenols, and each agent has been shown to exert antineoplastic effects against lung cancer. We hypothesize that combinations of GSE and MTE will additively enhance their anticancer effects against lung cancer. Materials and methodsThe anti-proliferative effects of GSE, MTE and combinations were evaluated in lung neoplastic cell lines. A dose range finding (DRF) study to determine safety, bioavailability and bioactivity, followed by human lung cancer xenograft efficacy studies were conducted in female nude mice with once daily gavage of leucoselect phytosome (LP), a standardized GSE, and/or siliphos, a standardized MTE. The roles of tumor suppressors miR-663a and its predicted target FHIT in mediating the additive, anti-proliferative effecs of GSE/MTE were also assessed. Key findingsGSE with MTE additively inhibited lung preneoplastic and cancer cell proliferations. Mice tolerated all dosing regimens in the DRF study without signs of clinical toxicity nor histologic abnormalities in the lungs, livers and kidneys. Eight weeks of LP and siliphos additively inhibited lung tumor xenograft growth. Plasma GSE/metabolites and MTE/metabolites showed that the combinations did not decrease systemic bioavailabilities of each agent. GSE and MTE additively upregulated miR-663a and FHIT in lung cancer cell lines; transfection of antisense-miR-663a significantly abrogated the anti-proliferative effects of GSE/MTE, upregulation of FHIT mRNA and protein. LP and siliphos also additively increased miR-663a and FHIT protein in lung tumor xenografts. SignificanceOur findings support clinical translations of combinations of GSE and MTE against lung cancer.

Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats.

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to “standard”, “cafeteria” and “cafeteria diet + GSPE” treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.

Green synthesis, characterization of procyanidin-mediated gold nanoparticles and its application in fluorescence detection of prazosin

Grape seed procyanidin extract was used to green synthesize AuNPs (OPC-AuNPs), in which procyanidin (OPC) accounted for 95% of total content. To improve the dispersion and uniformity of particle size, various conditions were optimized. The final OPC-AuNPs showed excellent stability and were characterized by a series of techniques. Owing to the good quenching properties of OPC-AuNPs, the fluorescence system of OPC-AuNPs and Rhodamine B (RB) mixture was established for prazosin testing. OPC-AuNPs could effectively quench fluorescence based on fluorescence resonance energy transfer (FRET). When prazosin and the testing system of OPC-AuNPs and RB mixture coexisted in the solution, prazosin would replace RB and competitively bond on the surface of OPC-AuNPs, thus RB was dissociated from OPC-AuNPs, resulting in the rapid recovery of fluorescence. This article provided a green, simple one-pot synthesis method for OPC-AuNPs and established a fast, sensitive, visible fluorescence system for prazosin detection which was successfully applied in real sample detection.

Grape seed proanthocyanidin extract ameliorates hepatic lipid accumulation and inflammation in grass carp (Ctenopharyngodon idella).

Hepatic lipid metabolism disorder due to excessive fat accumulation in fish is a significant problem in aquaculture. Studies have shown that grape seed procyanidin extract (GSPE) can regulate fish lipid metabolism and improve fish immunity. However, the mechanism is unclear. In this study, we used grass carp that stores excess fat in the liver as a model. In vitro, GSPE treatment of hepatocytes for 3h significantly decreased TG content, accompanied with decreased expression of SREBP-1c, FAS, and ACC and increased expression of PPARα, ATGL, and LPL. GSPE treatment for 1h significantly decreased expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1β, and NF-κB) and increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β1). In vivo, the administration of GSPE significantly reduced high-fat diet-induced increase of serum CHOL, TG, and HDL, but increased LDL content. GSPE treatment for 3h increased expression of ATGL and LPL, and significantly decreased the expression of HFD-fed-induced SREBP-1c, ACC, FAS, PPARγ, PPARα, and H-FABP. GSPE treatment for 3h also significantly decreased the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) and increased the expression of the anti-inflammatory cytokine IL-10. The expression levels of the lipogenic miRNAs, miR-33, and miR-122, were suppressed both in vivo and in vitro by GSPE. In summary, GSPE had hypolipidemic and potential anti-inflammatory effects in the liver, potentially mediated by miR-33 and miR-122.

Protective effects of grape seed procyanidin extract on intestinal barrier dysfunction induced by a long-term high-fat diet

Abstract Grape seed procyanidin extract (GSPE) can modulate intestinal dysfunction, however; the mechanism needs to be clarified. This study aims at investigating the beneficial effect of GSPE on intestinal epithelial integrity and its regulatory mechanism. The results showed that consumption of high-fat (HF) diet for 13 weeks increased intestinal permeability. GSPE (200 mg/kg·bw) treatment reduced the concentration of lipopolysaccharide (LPS) in the circulatory system. The expression of tight junction proteins increased in GSPE-treated rats. Moreover, GSPE treatment inhibited the expression of pro-inflammatory mediators. The flow cytometry results revealed that GSPE treatment significantly increased the proportion of CD4+ CD25+ Foxp3+ Tregs in gut-associated lymphoid tissue. GSPE modulated the composition of the gut microbiota and Spearman's correlation analysis revealed that the genera Anaerotruncus, Blautia, Oscillibacter, and Ruminococcaceae_UCG-004 were related to intestinal permeability indices. In conclusion, GSPE ameliorated intestinal barrier dysfunction in HF diet-fed rats, probably via the regulation of intestinal immune balance and intestinal microbiota.

Grape Seed Procyanidin Extract (GSPE) Improves Goat Sperm Quality When Preserved at 4 °C.

Simple SummaryArtificial insemination (AI) is widely used in goats, stimulating the development of semen preservation techniques. Oxidative stress is considered to be the main cause of sperm quality decline over time. In this study, we explored the effect of grape seed procyanidin extract (GSPE) during the liquid preservation of goat semen. The results showed that adding GSPE into the basic diluent enhanced sperm quality by eliminating oxidative stress. The most suitable concentration for the preservation of goat semen at 4 °C was 30 mg/L. This work suggests that promotes the viability of goat semen stored at low temperatures and provides a theoretical foundation for the development of more efficient diluents.Grape seed procyanidin extract (GSPE) has been shown to possess antioxidative effects. This experiment was designed to study the effect of GSPE during the liquid storage of goat semen. Semen samples were collected from six sexually mature goats. The samples were treated with different concentrations of GSPE (10, 30, 50, and 70 mg/L) in basic diluent and stored at 4 °C for 120 h; samples without GSPE were used as the control group. The results showed that sperm motility, acrosome membrane integrity, mitochondrial activity, plasma membrane integrity, total antioxidative capacity (T-AOC), catalase (CAT) activity, and superoxide dismutase (SOD) activity in the treatment groups were significantly higher than in the control group, whereas malondialdehyde (MDA) content was lower than in the control group (p < 0.05). In the treatment group, sperm quality in the 30 mg/L GSPE group was significantly higher than the other groups (p < 0.05). Furthermore, artificial insemination (AI) results showed that litter sizes were higher in the 30 mg/L GSPE group than in the control group (p < 0.05). In summary, this experiment showed that adding GSPE to the basic diluent improved sperm quality and that 30 mg/L of GSPE was the most suitable concentration for the liquid preservation of goat semen at 4 °C.

Illumina MiSeq sequencing reveals the effects of grape seed procyanidin on rumen archaeal communities in vitro.

ObjectiveThe present study explored the effects of grape seed procyanidin extract (GSPE) on rumen fermentation, methane production and archaeal communities in vitro.MethodsA completely randomized experiment was conducted with in vitro incubation in a control group (CON, no GSPE addition; n = 9) and the treatment group (GSPE, 1 mg/bottle GSPE, 2 g/kg dry matter; n = 9). The methane and volatile fatty acid concentrations were determined using gas chromatography. To explore methane inhibition after fermentation and the response of the ruminal microbiota to GSPE, archaeal 16S rRNA genes were sequenced by MiSeq high-throughput sequencing.ResultsThe results showed that supplementation with GSPE could significantly inhibit gas production and methane production. In addition, GSPE treatment significantly increased the proportion of propionate, while the acetate/propionate ratio was significantly decreased. At the genus level, the relative abundance of Methanomassiliicoccus was significantly increased, while the relative abundance of Methanobrevibacter decreased significantly in the GSPE group.ConclusionIn conclusion, GSPE is a plant extract that can reduce methane production by affecting the structures of archaeal communities, which was achieved by a substitution of Methanobrevibacter with Methanomassiliicoccus.

Dietary grape seed procyanidin extract protects against lead-induced heart injury in rats involving endoplasmic reticulum stress inhibition and AKT activation

To investigate the protective role of grape seed procyanidin extract (GSPE) against lead-induced heart injury and the possible molecular mechanism associated with this event, Wistar rats were orally given GSPE (200 mg/kg) daily with or without lead acetate (PbA) (0.5 g/L) in drinking water for 56 d. GSPE attenuated oxidative stress, heart dysfunction, and lead accumulation in lead-exposed rat hearts. Meanwhile, GSPE inhibited the protein kinase RNA-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α signaling pathway, and promoted protein kinase B (AKT) and glycogen synthase kinase 3β phosphorylation altered by lead, and regulated lead-activated apoptosis and its related signaling pathway. This study suggests that dietary GSPE ameliorates lead-induced heart injury associated with ER stress inhibition and AKT activation. Dietary GSPE may be a protector against lead-induced heart injury and a novel therapy for lead exposure.

Grape seed procyanidin extract inhibits adipogenesis and stimulates lipolysis of porcine adipocytes in vitro.

The objective of this article was to evaluate in vitro effect of grape seed procyanidin extract (GSPE) on differentiation, proliferation, and lipolysis of porcine adipocytes, providing a molecular basis for the use of GSPE in pig fat regulation. Primary preadipocytes isolated from subcutaneous adipose tissue of pigs were used as the in vitro cell model. Treatment of GSPE repressed preadipocyte differentiation, as evidenced by reduced lipid accumulation, decreased mRNA expressions of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid-binding protein 4 (FABP4), as well as enhanced expressions of preadipocyte factor-1. Activity of glycerol-3-phosphate dehydrogenase (GPDH), one of the most important enzymes in the pathway for triacylglycerol biosynthesis, was also decreased. Furthermore, GSPE could suppress preadipocyte proliferation by inducing G0/G1 cell cycle arrest and cell apoptosis. In porcine mature adipocytes, treatment with GSPE attenuated lipid content and GPDH activity, and the release of both free fatty acid and glycerol were enhanced; mRNA expressions of key lipolytic transcription factors, including hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), were elevated in GSPE-treated adipocytes. In summary, our results suggest GSPE inhibits porcine preadipocyte differentiation and proliferation and stimulates lipolysis of mature adipocytes, thus providing novel insights for further exploring the use of GSPE as a fat accumulation inhibitor.

Grape seed procyanidin extract protects against Pb-induced lung toxicity by activating the AMPK/Nrf2/p62 signaling axis

Lead (Pb) is one of the most relevant heavy metals contaminants which cause oxidative stress and threaten human health. The lung is one of the organs most severely damaged by Pb. In this study, we investigated the protective effect of grape seed procyanidin extract (GSPE) on Pb-induced lung injury in rats. We found that GSPE alleviated Pb-induced lung injury by relieving oxidative stress, reducing release of inflammatory factors, and inhibiting apoptosis. Furthermore, GSPE enhanced the antioxidant defense systems by activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway to promote downstream expression of heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1. The subsequent ubiquitin-binding protein p62 (sequestosome 1), a downstream target of Nrf2, formed a positive feedback loop with Nrf2 during oxidative stress responses. GSPE treatment resulted in activation of adenosine monophosphate-activated protein kinase (AMPK), which was highly involved in Nrf2 activation. Overall, our findings demonstrate that theprotective effect of GSPE on Pb-induced lung injury arises from activation of the AMPK/Nrf2/p62 signaling pathway, thus providing a new approach for treatment of Pb intoxication.

Grape seed procyanidins extract attenuates Cisplatin-induced oxidative stress and testosterone synthase inhibition in rat testes

ABSTRACTCisplatin (CIS) is widely applied for its antihematological malignancies properties and as antisolid tumors drugs. However, it could cause testicular damage related with oxidative stress and testosterone synthesis disorder. Studies reported that grape seed procyanidins extract (GSPE) could improve CIS induced-testes lesion via scavenging free radicals in animals, although its mechanisms were unclear. Therefore, the purpose of the present study was to explore the antagonistic mechanisms of GSPE on CIS-induced testes lesion. Rats were treated with 10 mg/kg by weight CIS by intraperitoneal injection singly on the 11th day, and different doses of GSPE were administrated via intragastric gavage for 15 days consecutively. The results showed that GSPE improved the pathological changes of testicular tissue, and the decreased concentrations of testosterone in serum induced by CIS. GSPE inhibited CIS-induced oxidative/nitrative stress, as well as increased the mRNA and protein levels of testosterone synthetase in rat testes. In conclusion, the main protection exerted by GSPE on CIS-induced testicular toxicity is related to its effects including suppressing oxidative/nitrative stress and up-regulating expression of testosterone synthetase.Abbreviations: CIS: Cisplatin; GSPE: grape seed procyanidins extract; LH: luteinizing hormone; FSH: follicle-stimulating hormone; STAR: steroidogenic acute regulatory protein; CYP11A1: P450 side chain cleavage enzyme; HSD3B1: 3β-hydroxysteroid dehydrogenase; CYP17A1: 17α-hydroxylase; HSD17B: 17β-hydroxysteroid dehydrogenase; ROS: reactive oxygen species; O2−: superoxide anion; H2O2: hydrogen peroxide; •OH: hydroxyl radicals; SOD: superoxide dismutase; CAT: catalase; GSH-Px: glutathione peroxidase; LPO: lipid peroxidation; 8-OHdG: 8-hydroxy-2-deoxyguanosine; HO-1: heme oxygenase-1; MT-1: metallothionein-1; NO: nitric oxide; ONOO-: peroxynitrite; NOS: nitric oxide synthases; nNOS: neuronal NOS; iNOS: inducible NOS; eNOS: endothelial NOS; MDA: malondialdehyde; GSH: glutathione; T-AOC: total antioxidant capacity; TNOS: total nitric oxide synthases; Lhcgr: luteinizing hormone receptor; Scarb1: lipoprotein-receptor; Cyp19a1: 19α-hydroxylase; ELISA: enzyme linked immunosorbent assay; RT-qPCR: reverse transcription-quantitative polymerase chain reaction; PAS: periodic acid–Schiff; MTs: Metallothioneins; cAMP: cyclic adenosine monophosphate; cDNA: complementary DNA; RIPA: radioimmunoprecipitation buffer; PMSF: phenylmethanesulfonyl fluoride; PVDF: polyvinylidenedifluoride; β-actin: beta-actin

Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity.

MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA and protein (p21) levels. Transfection of miR-106b mimics reversed the up-regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative and anti-invasive properties in lung cancer cells. Oral gavage of leucoselect phytosome (LP), a standardized GSE to athymic nude mice down-regulated MIR106B mRNA and miR-106b expressions, and increased CDKN1A mRNA expression in tumor xenografts, correlating to significant reduction of tumor growth. To assess bioavailability, GSE and metabolites in plasma levels, between 60–90 minutes after gavage of LP were measured by LC/MS at treatment week 4 and 8. A novel bioactivity assay was also developed using lung homogenates from treated mice co-cultured with human lung cancer cells. LP-treated mouse lung homogenates significantly reduced proliferations of various lung cancer cells. Our findings reveal novel antineoplastic mechanisms by GSE, further define the pharmacokinetics and pharmacodynamics of LP, and support the continued investigation of LP against lung cancer.

Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation

Lead-induced hepatotoxicity is characterized by an extensive oxidative stress. Grape seed procyanidin extract (GSPE) possesses abundant biological activities. Herein, we investigated the protective role of GSPE against lead-induced liver injury and determined the potential molecular mechanisms. In vivo, rats were treated with/without lead acetate (PbAc) (0.05%, w/v) in the presence/absence of GSPE (200 mg/kg). In vitro, hepatocytes were pretreated with/without GSPE (100 μg/ml) in the presence/absence of PbAc (100 μM). PbAc administration to rats resulted in anemia, liver dysfunction, lead accumulation in the bone and liver, oxidative stress, DNA damage and apoptosis. GSPE significantly attenuated these adverse effects, except lead accumulation in liver. GSPE also decreased the expression of miRNA153 and increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and levels of its downstream protein, and protein kinase B (AKT) phosphorylation in PbAc-induced liver injury. In primary hepatocytes treated with PbAc, GSPE increased hepatocyte viability and decreased lactate dehydrogenase release and reactive oxygen species levels. Dietary GSPE attenuated PbAc-induced liver injury in rats via an integrated mechanism associated with the miRNA153 and AKT/glycogen synthase kinase 3 beta/Fyn-mediated Nrf2 activation.

Maternal intake of grape seed procyanidins during lactation induces insulin resistance and an adiponectin resistance-like phenotype in rat offspring

Previously, we demonstrated that a grape seed procyanidin extract (GSPE) supplementation in pregnant and lactating rats exerted both healthy and deleterious programming effects on their offspring. Here, we evaluated whether the administration of GSPE during lactation (100 mg.kg−1.day−1) in rats elicited beneficial effects in their normoweight (STD-GSPE group) and cafeteria-fed obese (CAF-GSPE group) adult male offspring. STD-GSPE and CAF-GSPE offspring showed increased energy expenditure and circulating total and high-molecular-weight adiponectin. However, these rats showed hyperinsulinemia, decreased insulin sensitivity, increased insulin resistance, down-regulated mRNA levels of adiponectin receptors in inguinal white adipose tissue (Adipor1 and Adipor2) and soleus muscle (Adipor2), and decreased levels of phosphorylated AMPK, the downstream post-receptor target of adiponectin, in the soleus muscle. These deleterious effects could be related to an increased lipid transfer to the pups through the milk, since GSPE-supplemented dams displayed decreased fat content and increased expression of lipogenic genes in their mammary glands, in addition to increased circulating total adiponectin and non-esterified free fatty acids. In conclusion, maternal intake of GSPE during lactation induced insulin resistance and an adiponectin resistance-like phenotype in their normoweight and obese offspring. These findings raise concerns about the possibility of using GSPE as a nutraceutical supplement during this period.

Reduction of oxidative damages induced by titanium dioxide nanoparticles correlates with induction of the Nrf2 pathway by GSPE supplementation in mice

Titanium dioxide nanoparticles (TiO2 NPs) are widely used to additives in cosmetics, pharmaceuticals, paints and foods. Recent studies have demonstrated that TiO2 NPs increased the risk of cancer and the mechanism might relate with oxidative stress. Grape seed procyanidin extract (GSPE) is a natural compound which has been demonstrated to possess a wide array of pharmacological and biochemical actions, including anti-inflammatory, anti-carcinogenic, and antioxidant properties. Our data show that GSPE prevents the changes of histopathology and biomarkers in heart, liver and kidney that occur in mice exposed to TiO2 NPs. After pretreatment with GSPE, the DNA damage, reactive oxygen species (ROS) generation and malondialdehyde (MDA) content in mice exposed to TiO2 NPs had statistically significant decreases in dose dependent manners. GSPE increased the expression of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), NAD(P)H dehydrogenase[quinine] 1(NQO1), heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC). We conclude that grape seed procyanidin extract prevents the majority of tissue and molecular damage resulting from nanoparticle treatment. The protective effect of GSPE may be due to its strong antioxidative activities which related with the activated Nrf2 and its down-regulated genes including NQO1, HO-1 and GCLC.

Determination of the Bioactive Components in a Grape Seed Procyanidin Extract Responsible for Enhanced Farnesoid X Receptor Transactivation

Dietary procyanidins are beneficial for maintaining health. Grape seed procyanidin extract (GSPE) in particular has been shown to regulate cholesterol and triglyceride (TG) homeostasis in vivo (1–5). We have identified several underlying molecular mechanisms by which GSPE decreases serum TG levels, including farnesoid x receptor (FXR)‐dependent decreased hepatic triglyceride synthesis, inhibition of enterohepatic bile acid recirculation and increased hepatic TG catabolism (3–5). Furthermore, we identified GSPE as a histone deacetylase (HDAC) inhibitor, leading to enhanced peroxisome proliferator‐activated receptor alpha (PPARα) target‐gene transcription and increased fatty acid β‐oxidation (6). During our initial investigations we discovered that GSPE acts as a co‐agonist ligand for FXR (2). The present study was designed as a follow‐up to this initial observation and aimed to identify which component (or components) within GSPE are responsible for the observed FXR‐dependent co‐agonist activity. GSPE was fractionated by column chromatography to separate compounds based on molecular size (n=3). The degree of polymerization for each fraction was determined by high performance liquid chromatography. Using a cell‐based transient transfection assay, each fraction was tested in combination with the bile acid, chenodeoxycholic acid (CDCA), to assess its ability to increase FXR transactivation (n=3, analyzed in triplicate), and compared to the effect seen with GSPE. Five different fractions from each column consistently enhanced FXR transactivation and were subsequently analyzed by mass spectrometry (MS). The MS results show that the fractions that enhance FXR transactivation are enriched in dimers and dimer gallates. Ultimately, this study facilitates enhanced understanding regarding the observed GSPE‐mediated FXR‐dependent regulatory effects on metabolic homeostasis observed in vivo.Support or Funding InformationUSDA NIFA Hatch Project NEV0738; USDA NIFA Multi‐state Project W‐3122: Beneficial and adverse effects of natural chemicals on human health and food safety; USDA NIFA Hatch Project NEV0749; A grant from the National Institute of General Medical Sciences (P20GM103440) from the National Institutes of Health.

GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney.

Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.

Front cover: A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target-gene expression

Front cover: A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target-gene expression