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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background The 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. Results After 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. Conclusions NaB 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.

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. [ABSTRACT FROM AUTHOR]

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.

This study aimed to elucidate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative stress (OS), antioxidant enzymes, free radicals and cytokines in the pancreas of T1DM rats. Two-month-old Wistar rats were assigned to the control (CON), CON + GSPE (CON + PA), diabetics (STZ, 60 mg/kg b.w.), diabetes + GSPE (STZ + PA), diabetes + insulin (STZ + INS, 3 U/day) and diabetics + GSPE and INS (STZ + INS + PA) groups. GSPE (75 mg/kg b.w.) was administered daily either alone or with INS for 8 weeks. Glutathione was lowest in diabetics while it increased in the STZ + INS + PA (p <.001) group, similar to catalase activity (p <.05). Hydrogen peroxide, superoxide and lipid peroxidation increased with iNOS, TNF-α and IL-1β in the diabetic pancreases, while GSPE decreased (p <.001). Further, reduced β-cells/islet number was improved in diabetics (p <.001) with treatment. This study suggests that GSPE with INS is effective in minimising OS and pancreatic degeneration in T1DM rats. [ABSTRACT FROM AUTHOR]

Background: The 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. Results: After 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. Conclusions: NaB 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. [ABSTRACT FROM AUTHOR]

Objective To observe the preventive effect of intragastric pre-administration of grape seed proanthocyan⁃ idin extract (GSPE) on rats with acute renal injury induced by contrast media and to explore its possible mechanism. Methods Fifty SD obese rats were intraperitoneally injected with 1% STZ (40 mg/kg), of which，41 diabetes model rats were successfully established. They were randomly divided into five groups； there were 8 rats in the diabetes mellitus (DM) group，9 rats in the contrast medium (CM) group，8 rats in the low-dose GSPE group，8 rats in the medium-dose GSPE group, and 8 rats in the high-dose GSPE group. Another 10 obese rats were taken as the blank control (NC) group, and 1 mL/kg of citric acid buffer was intraperitoneally injected. The rats in the low-, medium- and high-dose GSPE groups were given 50，250 and 500 mg/kg GSPE by gavage once a day for three consecutive days, and the rats on the third day were given iohexol (1. 8 g I/kg) by tail vein at the time of 24 hours of gavage. The rats in NC group, DM group and CM group were given 10 mL/kg normal saline once a day. When the rats were given 10 mL/kg normal saline for 24 h on the third day, the rats in the NC group and DM group were given 5 mL/kg normal saline through the tail vein, and the rats in the CM group were given iohexol (1. 8 g I/kg) through the tail vein. At 48 h after the last administration, blood was taken from their tails of rats in each group, and serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. Rats in each group were killed after the blood was taken. The renal tissue was taken to detect the oxidative stress indicators of renal tissues, such as superoxide dismutase (SOD) and malondialdehyde (MDA). The apoptosis index of renal tubular epithelial cells in each group was measured by in situ nick end labeling (TUNEL) method； Western blotting was used to detect the nuclear factor E2-associated factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) pathway-related quinone oxidoreductase 1 (NQO1), heme monooxygenase-1 (HO-1), Nrf2, and Keap1 proteins in the renal tissues of rats in each group. Results Compared with the NC group, the levels of SCr and BUN in the CM group and low-dose GSPE group were higher (all P<0. 05). Compared with the CM group, the levels of SCr and BUN in the NC group, DM group and low-, medium- and high-dose GSPE groups were lower (all P<0. 05). Compared with the low-dose GSPE group, the levels of SCr and BUN in the medium-dose and high-dose GSPE groups were lower (all P<0. 05). Compared with the NC group, the levels of SOD in the renal tissue homogenate of the DM group, CM group, low-dose and medium-dose GSPE groups were lower, and the levels of MDA in the renal tissue homogenate of the DM group, CM group and low-dose GSPE group were higher (all P<0. 05). Compared with the CM group, the levels of SOD in the DM group, low-dose, medium-dose and high-dose GSPE groups were higher, and the levels of MDA were lower (all P<0. 05). Compared with the CM group, the apoptosis indices of renal tubular epithelial cells in the medium-dose and high-dose GSPE groups were lower (all P< 0. 05). Compared with NC group, the relative expression levels of Nrf2, HO-1, and NQO1 proteins in the renal tissues of rats in the CM group were lower, while the relative expression of Nrf2, HO-1 and NQO1 proteins in the renal tissues of rats in the medium-dose and high-dose GSPE group were higher (all P<0. 05). Compared with the CM group, the relative ex⁃ pression levels of Nrf2, HO-1, and NQO1 proteins in the kidney tissues of rats in the low-dose, medium-dose and highdose GSPE group were higher (all P<0. 05). Compared with the medium-dose group, the relative expression levels of Nrf2, HO-1, and NQO1 proteins in the kidney tissues of rats in the low-dose group were lower (all P<0. 05). Conclusion GSPE can alleviate renal injury in diabetes rats injected with contrast agent through tail vein, and the optimum concentration is 500 mg/kg. GSPE may prevent acute renal injury in contrast-induced diabetes rats by activating Nrf2-Keap1 signaling pathway. [ABSTRACT FROM AUTHOR]

Aristolochic acid is internationally recognized as a carcinogen. It has been shown that the main toxic mechanism of aristolochic acid on the liver and kidney is the induction of ROS-induced oxidative stress damage. To investigate whether proanthocyanidins (GSPE), a natural antioxidant product from grape seed extract, could antagonize AA-I-induced liver injury. Thirty-two SD rats were selected and divided into aristolochic acid exposure group (AA-I), normal control group, GSPE group and GSPE intervention group. The protective effects of GSPE on AA-I liver injury were evaluated by examining the body weight, liver index, liver function and liver pathological sections of rats. The results of body weight, liver index, liver function and liver pathological sections of rats showed that GSPE had antagonistic effects on AA-I-induced liver injury. antioxidant enzyme activity in the GSPE intervention group was significantly higher than that in the aristolochic acid group, apoptotic cells were significantly lower than that in the aristolochic acid group, protein and mRNA expression of PI3K-AKT and BCL-2 were significantly higher than that in the aristolochic acid group, BAX, The protein and mRNA expression of BAX, CASPAES-3, CASPAES-9 were significantly lower than those of the aristolochic acid group. GSPE can antagonize aristolochic acid-induced hepatotoxicity, and its mechanism of action is to antagonize aristolochic acid I-induced liver injury by inhibiting PI3K-AKT pathway-mediated hepatocyte apoptosis. [ABSTRACT FROM AUTHOR]

Mitochondrial biogenesis and dynamics are associated with renal mitochondrial dysfunction and the pathophysiological development of diabetic kidney disease (DKD). Decreased p66Shc expression prevents DKD progression by significantly regulating mitochondrial function. Grape seed proanthocyanidin extract (GSPE) is a potential therapeutic medicine for multiple kinds of diseases. The effect of GSPE on the mitochondrial function and p66Shc in DKD has not been elucidated. Hence, we decided to identify p66Shc as a therapeutic target candidate to probe whether GSPE has a renal protective effect in DKD and explored the underlying mechanisms. Methods. In vivo, rats were intraperitoneally injected with streptozotocin (STZ) and treated with GSPE. Biochemical changes, mitochondrial morphology, the ultrastructure of nephrons, and protein expression of mitochondrial biogenesis (SIRT1, PGC-1α, NRF1, TFAM) and dynamics (DRP1, MFN1) were determined. In vitro, HK-2 cells were transfected with p66Shc and treated with GSPE to evaluate changes in cell apoptosis, reactive oxygen species (ROS), mitochondrial quality, the protein expression. Results. In vivo, GSPE significantly improved the renal function of rats, with less proteinuria and a lower apoptosis rate in the injured renal tissue. Besides, GSPE treatment increased SIRT1, PGC-1α, NRF1, TFAM, and MFN1 expression, decreased p66Shc and DRP1 expression. In vitro, overexpression of p66Shc decreased the resistance of HK-2 cells to high glucose toxicity, as shown by increased apoptosis and ROS production, decreased mitochondrial quality and mitochondrial biogenesis, and disturbed mitochondrial dynamic homeostasis, ultimately leading to mitochondrial dysfunction. While GSPE treatment reduced p66Shc expression and reversed these changes. Conclusion. GSPE can maintain the balance between mitochondrial biogenesis and dynamics by negatively regulating p66Shc expression. [ABSTRACT FROM AUTHOR]

A trial was conducted to evaluate the effect of dietary grape seed proanthocyanidin extract (GSPE) on goldfish, Carassius auratus. In this regard, GSPE was added to a basal diet at four levels including 0, 200, 400, and 600 mg/kg to produce four experimental diets including control, GSPE200, GSPE400, and GSPE600. Three hundred and sixty goldfish (3.75 ± 0.1 g) were stocked in twelve 100 L rectangular tanks (30 fish per tank) and fed with the experimental diets three times a day for nine weeks. During the experimental trial, water temperature was 26.7–28.5°C. The weight gain and specific growth rate in the fish fed with GSPE supplemented diets were higher than the control, meanwhile feed conversion ratio value in these groups decreased compared to the control. Fish fed GSPE-supplemented diets had lower fillet lipid (10–19%), but higher protein levels (7–15%) compared to the control. The levels of serum triglyceride, alanine aminotransferase and aspartate aminotransferase in the fish fed GSPE-supplemented diets were decreased compared to the control group. The highest and lowest levels of serum glucose, and ALP were in the fish fed with control and GSPE600 diets, respectively. The skin mucosal lysozyme activity (24–38%) and protein level (70–96%) were higher in fish fed GSPE-supplemented diets than the control. The highest, and lowest liver antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase were observed in GSPE 600 and control groups, respectively. The findings of the present study indicated that supplementing 400 mg/kg GSPE in diet can improve growth and health condition in goldfish. [ABSTRACT FROM AUTHOR]

Objective： To explore the improvement effects of grape seed proanthocyanidin extract (GSPE) on the periodontal inflammation in the diabetic periodontitis rats, and to clarify its mechanism. Methods：Forty male SD rats were randomly divided into control group, diabetic periodontitis model group (model group), low dose (100 mg·kg－1) of GSPE group and high dose (200 mg·kg－1) of GSPE group； there were 10 rats in each group. Except for control group, the rats in other groups were used to establish the diabetic periodontitis models by periodontal ligation combined with intraperitoneal injection of streptozotocin (STZ). After the successful establishment of the models, the rats in low and high doses of GSPE groups were given 100 and 200 mg·kg－1 GSPE, respectively, while the rats in control group and model group were given the same amount of normal saline once a day for 8 weeks. The general situation of the rats and the changes of blood glucose levels were observed, the pathomorphology of periodontal tissue of the rats in various groups were observed by HE staining, the alveolar bone absorption of the rats in various groups was measured, the activities of superoxide dismutase (SOD) and the catalase (CAT) and the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in periodontal tissue of the rats in various groups were detected by related kits. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) in serum of the rats in various groups. The expression levels of Toll-like receptor 4 (TLR4) and nuclear factor- κB (NF- κB) proteins in periodontal tissue of the rats in various groups were detected by Western blotting method. Results：Compared with control group, the rats in model group showed obvious symptoms of“ three more and one less”；the level of blood glucose of the rats was increased obviously (P< 0. 05), the inflammatory cells were infiltrated in periodontal connective tissue, periodontal tissue was damaged, and the alveolar bone absorption amount was increased (P<0. 05)；the activities of SOD and CAT in periodontal tissue were significantly decreased (P<0. 05), the levels of ROS and MDA were significantly increased (P<0. 05), the levels of TNF- α, IL-1β and IL-6 in serum were significantly increased (P<0. 05), and the expression levels of TLR4 and NF- κ B proteins were significantly increased (P<0. 05). Compared with model group, the general condition of the rats in low and high doses of GSPE groups was obviously improved, the levels of blood glucose were reduced (P<0. 05), periodontal tissue damage was obviously reduced, the alveolar bone absorption amounts were reduced (P<0. 05), the activities of SOD and CAT in periodontal tissue were significantly increased (P<0. 05), the levels of ROS and MDA were significantly decreased (P<0. 05), the levels of TNF- α, IL-1β and IL-6 in serum were significantly decreased (P<0. 05), and the expression levels of TLR4 and NF-κB proteins were significantly decreased (P<0. 05). Compared with low dose of GSPE group, the activities of SOD and CAT in periodontal tissue of the rats in high dose of GSPE group were significantly increased (P<0. 05), the levels of ROS and MDA were significantly decreased (P<0. 05), the levels of TNF-α, IL-1β and IL-6 in serum were significantly decreased (P<0. 05), and the expression levels of TLR4 and NF- κB proteins were significantly decreased (P<0. 05). Conclusion：GSPE can improve the periodontal inflammation in the diabetic periodontitis rats, and its mechanism may be related to regulating the TLR4 and NF- κB signaling pathway in periodontal tissue. [ABSTRACT FROM AUTHOR]

The current study was aimed to examine the effect of grape seed proanthocyanidin extract (GSPE) on regulating lipid metabolism of American eels. A total of six cement tanks of fish were randomly divided into a control group fed with a commercial diet and a GSPE group fed with a commercial diet supplemented 400 mg/kg GSPE. There were three replicates in each group. Results suggested that GSPE could decrease the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increase the high-density lipoprotein cholesterol level in serum. GSPE might regulate lipid metabolism through upregulating linoleic acid metabolism and arachidonic acid metabolism along with downregulating metabolisms of phenylalanine, tyrosine, and tryptophan biosynthesis and valine, leucine, and isoleucine biosynthesis. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to evaluate the association between grape seed proanthocyanidin extract (GSPE) and rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) and to investigate whether GSPE induces cell death in RA-FLSs. Materials and methods: The FLSs were isolated from RA synovial tissues. Cell viability and cell cycle staging were analyzed using a hemocytometer and flow cytometry. Caspase 3 and poly (ADP-ribose) polymerase (PARP) proteins were analyzed using Western blotting with z-VAD-fmk. Protein LC3 and polyubiquitin-binding protein p62 that were degraded by autophagy were evaluated using Western blotting with 3-methyladenine and chloroquine. Reactive oxygen species (ROS) were also evaluated. Results: When RA-FLSs were treated with GSPE, cell viability decreased, the number of cells in sub-G1 and G2/M phases increased, and the expression of pro-PARP and pro-caspase 3 proteins decreased in a concentration-dependent manner. This result was offset, when the cells were co-treated with the pan-caspase inhibitor z-VAD-fmk. The reduced cell viability, increased expression of LC3-II protein, and reduced expression of p62 protein with GSPE treatment were offset, when RA-FLSs were co-treated with GSPE and autophagy inhibitors 3-methyladenine and chloroquine. The level of ROS in RA-FLSs treated with GSPE was significantly lower than treatment with N-acetyl-cysteine, a ROS inhibitor. Conclusion: Our study results show that GSPE induces apoptotic and autophagic cell death and inhibites reactive oxygen species in RA-FLSs. [ABSTRACT FROM AUTHOR]

Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment.

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent. [Display omitted] • GSPE can mitigate IR-induced hematopoietic injury. • GSPE reduces ROS level and DNA damage in irradiated HSPCs. • Foxo1 deficiency leads to increased sensitivity of HSPCs to irradiation. • GSPE specifically upregulates the expression of Foxo1 to decrease IR-induced injury in HSPCs. [ABSTRACT FROM AUTHOR]

Myocardial infarction is one of the most serious fatal diseases in the world, which is due to acute occlusion of coronary arteries. Grape seed proanthocyanidin extract (GSPE) is an active compound extracted from grape seeds that has anti-oxidative, anti-inflammatory and anti-tumor pharmacological effects. Natural products are cheap, easy to obtain, widely used and effective. It has been used to treat numerous diseases, such as cancer, brain injury and diabetes complications. However, there are limited studies on its role and associated mechanisms in myocardial infarction in mice. This study showed that GSPE treatment in mice significantly reduced cardiac dysfunction and improved the pathological changes due to MI injury. In vitro, GSPE inhibited the apoptosis of H9C2 cells after hypoxia culture, resulting in the expression of Bax decreased and the expression of Bcl-2 increased. The high expression of p-PI3K and p-AKT was detected in MI model in vivo and in vitro. The use of the specific PI3K/AKT pathway inhibitor LY294002 regressed the cardio-protection of GSPE. Our results showed that GSPE could improve the cardiac dysfunction and remodeling induced by MI and inhibit cardiomyocytes apoptosis in hypoxic conditions through the PI3K/AKT signaling pathway.

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Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Grape seed proanthocyanidin extract (GSPE) is a popular dietary supplement that has been shown to have a wide variety of beneficial actions. First brought into public consciousness as one of the key active components of red wine, proanthocyanidins are bioavailable in plasma and have potent antioxidant activity. Their free radical scavenging properties are greater than popular antioxidants such as vitamins C and E, and GSPE shows a superior ability to protect cells against lipid peroxidation and DNA fragmentation. GSPE also exhibits cardioprotective effects by preserving myocardial function after ischemia and reperfusion, and reduces total cholesterol levels in combination with the anti-aging supplement chromium polynicotinate through a synergistic effect. GSPE has been shown to inhibit the growth of cancer cells, while encouraging growth in normal human cells and protecting normal human cells against the toxicity of chemotherapeutic agents. Proposed mechanisms for GSPE's activity towards cancer cells include GSPE-modulated upregulation of bcl-Xs and JNK genes leading to apoptosis, as well as downregulation of bcl-Xl expression and mitogenic signaling to promote cell growth. Toxicity and mutation studies have demonstrated the safety of GSPE, supporting the use of GSPE as a health supplement.

The dorsomedial prefrontal cortex (dmPFC) is critical for working memory, which declines with age. The mechanisms for aging dmPFC are oxidative stress, antioxidant defense and anatomical alterations. This study was carried out to test whether swimming training and grape seed proanthocyanidin extract (GSPE) are suitable interventions for curtailing free radical generation in the dmPFC in middle-aged male rats. The results indicated that superoxide and hydrogen peroxide increased in the middle-aged, as did lipid and protein oxidations, while superoxide dismutase and catalase activity decreased. There were positive correlations between age and lipofuscin. Importantly, the rats experienced reductions in neuronal number, volume and density in the dmPFC. Rats under combined interventions displayed more alleviation of the age changes than rats with single interventions suggesting the possibilities of utilizing GSPE as a functional supplement in conjunction with swimming exercise towards improving neuronal survivability, and preventing cognitive decline beyond middle-age.

[Display omitted] • GSPE reduced CSE-induced increase in ROS and apoptosis levels in mouse lungs and AECs. • GSPE lowered Bax/Bcl-2 ratio, protecting against CSE-induced epithelial cell apoptosis. • GSPE ameliorated lung inflammation by reducing the number of inflammatory cells. • GSPE improved COPD phenotypes: airspace enlargement and alveolar wall damage. 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. [ABSTRACT FROM AUTHOR]

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload. [ABSTRACT FROM AUTHOR]

To evaluate the effects of osteoporosis induced by dexamethasone (DEX) and assess the possible anti-osteoporotic effect of grape seed proanthocyanidin extract (GSPE) on bone tissue of female albino rats. Thirty-two female albino rats divided into four groups: normal, DEX control, orally treated with GSPE (400 mg/kg) 7 days before DEX-injection, and orally treated with GSPE (400 mg/kg) after DEX-injection for 4 weeks. Animals received 0.1 mg/kg of dexamethasone intramuscularly three times per week for 4 weeks. After 4 weeks, the animals were sacrificed, and blood samples were collected for determination of biochemical investigations. Right, and left femurs were excised for biochemical and histological examination. DEX-induced remarkable elevation in the activities of alkaline phosphatase and acid phosphatase, and level of blood urea nitrogen (BUN) with concomitant declined in electrolyte profile (Na, K, and Ca). Lipid peroxidation marker (MDA) was significantly elevated in DEX-induced animals with concomitant declined in glutathione (GSH) content and superoxide dismutase (SOD) activity. Administration of GSPE significantly alleviates serum activities of alkaline phosphatase and acid phosphatase and blood urea nitrogen (BUN) level. GSPE attenuated DEX-induced oxidative stress and restored the antioxidant defenses. In addition, GSPE improved femur bone histological structure alterations induced by dexamethasone. GSPE possessed antioxidant potentials, and anti-osteoporotic effects against glucocorticoids induced osteoporotic rats by the maintenance of calcium homeostasis and scavenging of the free radicals which in turn induced the lipid peroxidation. Thus, GSPE may be a candidate as an anti-osteoporotic agent. [ABSTRACT FROM AUTHOR]

Lead, a pervasive environmental hazard worldwide, causes a wide range of physiological and biochemical destruction, including metabolic dysfunction. Grape seed proanthocyanidin extract (GSPE) is a natural production with potential metabolic regulation in liver. This study was performed to investigate the protective role of GSPE against lead-induced metabolic dysfunction in liver and elucidate the potential molecular mechanism of this event. Wistar rats received GSPE (200 mg/kg) daily with or without lead acetate (PbA, 0.5 g/L) exposure for 56 d. According to biochemical and histopathologic analysis, GSPE attenuated lead-induced metabolic dysfunction, oxidative stress, and liver dysfunction. Liver gene expression profiling was assessed by RNA sequencing and validated by qRT-PCR. Expression of some genes in peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway was significantly suppressed in PbA group and revived in PbA + GSPE group, which was manifested by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated by western blot analysis. This study supports that dietary GSPE ameliorates lead-induced fatty acids metabolic disturbance in rat liver associated with PPARα signaling pathway, and suggests that dietary GSPE may be a protector against lead-induced metabolic dysfunction and liver injury, providing a novel therapy to protect liver against lead exposure. [ABSTRACT FROM AUTHOR]

Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μM N-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.

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The present study investigated whether grape seed proanthocyanidin extract (GSPE) can attenuate varicocele-induced testicular oxidative injury through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant pathway. A varicocele model in rats was established by partial ligation of the left renal vein. Following 4 weeks of GSPE administration, the decreased sperm count and motility and other pathological changes caused by varicocele were significantly alleviated, as indicated by the results of computer-assisted sperm analysis and hematoxylin and eosin staining. In addition, the decreased antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activity and elevated oxidative stress level were partially reversed by administration of GSPE. Furthermore, the apoptotic level of the testis induced by varicocele was decreased by the GSPE treatment, according to terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Additionally, the expression of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 and cleaved caspase-3, were also affected by GSPE. GSPE activated Nrf2, which is a key antioxidative transcription factor, with elevation of the downstream factor hemeoxygenase-1. These findings suggest that GSPE can ameliorate abnormal spermatogenesis and testicular injury in varicocele rats, potentially due to its antioxidative activity and ability to activate the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy has long been recognized as a microvascular disease, however, recent research has indicated that diabetic retinopathy may also be considered a neurodegenerative disease. The elucidation of the molecular mechanisms underlying the development of diabetic retinopathy is imperative for the development of preventive and treatment strategies for patients with diabetes. In the present study, grape seed proanthocyanidin extract (GSPE) was used to upregulate the expression of thioredoxin (Trx), in order to evaluate its potential as a novel agent for the prevention and treatment of neurodegenerative diseases, including diabetic retinopathy. Hematoxylin and eosin staining was performed to observe the morphology of retinal neurons, whereas flow cytometry and terminal deoxynucleotidyl transferase 2'‑deoxyuridine, 5'‑triphosphate nick‑end labeling were employed to investigate cellular apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to assess the mRNA and protein expression of target proteins in order to investigate the underlying molecular mechanisms. In vivo, it was found that the photoreceptor cell was damaged in diabetic mice but following GSPE treatment, the process could be inhibited. In vitro, the results of the current study demonstrated that, under hyperglycemic culture conditions, the expression of 78 kDa glucose‑regulated protein, which is an endoplasmic reticulum stress marker, was upregulated. In addition, the expression of Trx was downregulated and cell apoptosis was enhanced. Notably, treatment with GSPE was revealed to inhibit the neurodegenerative process induced by hyperglycemia. However, treatment with the Trx inhibitor PX12 in combination with GSPE was demonstrated to potentiate apoptosis compared with GSPE treatment alone under hyperglycemic conditions. Furthermore, the protein expression of apoptosis signal‑regulating kinase (ASK) 1 and Trx‑interacting protein (Txnip) was also upregulated by hyperglycemia, whereas GSPE was revealed to counteract this upregulation. In conclusion, the results of the present study indicate that Trx may be implicated in the mechanisms underlying the protective effects of GSPE against hyperglycemia‑induced cell degeneration and apoptosis. The molecular mechanisms may also involve inhibition of the activation of the Trx/ASK1/Txnip signaling pathway. [ABSTRACT FROM AUTHOR]

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens. [ABSTRACT FROM AUTHOR]

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens. [ABSTRACT FROM AUTHOR]

Grape seed proanthocyanidin extract (GSPE) is known to be effective on broad spectrum of biological pathways in living organisms including oxidative stress. The present study aimed to investigate the effects of proanthocyanidin on preneoplastic lesions and liver cancer induced in rats by Diethylnitrosamine (DEN). 7–8 Week old male Sprague Dawley (S.D.) rats were divided into six groups: The 1st group received no treatment and were −ve controls, the 2nd were treated with a single dose of DEN 200 mg/kg intraperitoneally (i.p.) and served as +ve control group. The 3rd and 4th groups were injected with the same dose of DEN as in group 2 and then post treated with 300 or 150 mg/kg/b.wt./day GSPE by intrgastroluminal gavage (i.g.) respectively until the end after the 22 weeks. Groups 5 and 6 were treated with the same doses of GSPE as in groups 3 and 4 respectively without DEN administration. The results showed that the immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling indexes (PCNA LI%) were significantly inhibited in liver tissues and tumors by both treatments of GSPE. Furthermore, treatment with GSPE has modified the liver tissue oxidative stress markers levels of SOD, CAT, GSH, GST, GPx, GR and MDA changed by DEN. In conclusion, GSPE has a sufficient therapeutic effect against liver carcinogenesis through their free radical scavenging, inhibition of cellular proliferation. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB1-induced immunotoxicity and oxidative stress via NF-κB and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control); 2. Basal diet + AFB1 1mg/kg contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB1 1 mg/kg + GSPE 250 mg/kg (AFB1 + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1β, IL-10, and IL-6 induced by AFB1. Similarly, GSPE + AFB1 treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the splenic tissue compared to the AFB1 treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of IκBα protein induced by AFB1. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB1 group. Taken together, GSPE alleviates AFB1-induced immunotoxicity and oxidative damage by inhibiting the NF-κB and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB1-induced immunotoxicity and oxidative damage.

• An efficient degradation of GSPE was achieved using DTT as the novel nucleophile. • Degradation conditions were ascertained by the optimization of BP neural network. • Six novel flavan-3-ol-dithiothreitol conjugates were obtained. • Degradation products showed protective effect against A β -induced neurotoxicity in vitro. Dithiothreitol (DTT) was adopted as a nucleophile to develop a new acid-catalyzed degradation method for grape seed proanthocyanidin extraction (GSPE). Backpropagation neural network and Box-Behnken design were employed and compared to establish the optimized degradation conditions. GSPE was reacted with DTT at a ratio of 1:1 under mild conditions with 0.14 M HCl at 40.8 °C for 60 min. Three monomeric proanthocyanidins and six novel flavan-3-ol-DTT conjugates consisting of three pairs of diastereomers were simultaneously obtained with a high yield (929 mg/g). All the degradation products showed protective effects against A β 25-35 -induced neurotoxicity in PC-12 cells and prevented A β 25-35 aggregation based on the results from MTT and thioflavin T fluorescence assays, respectively. Detailed intermolecular interactions leading to the prevention of Aβ 25-35 aggregation were elucidated using molecular docking. This work would provide new compounds from functional foods that can be explored for their neuroprotective potential. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of grape seed proanthocyanidin extract (GSPE) adjuvant therapy on sleep quality of patients with obstructive sleep apnea-hvpopnea syndrome (OSAHS) and its mechanism. Methods Totally 101 OSAHS patients were randomly divided into low-dose GSPE group (34 cases) , high-dose GSPE group (33 cases) and control group (34 cases). The control group was treated with continuous positive airway pressure ventilation. Patients in the low-dose and high-dose groups were given orally GSPE 1 and 2 seeds/ time, twice a day, and for 8 weeks. All subjects in the three groups received polysomnography before and after treatment. We recorded the longest time breathing low ventilation (MHT) , hypopnea index (H111) , the longest apnea time (LAT) , apnea index ( Al) , respiratory disturbance index ( RD1) , the lowest oxygen saturation ( LSaO2 ) , rapid eye movement (REM) , and micro-awakening index (M-AI). The degree of subjective sleepiness was scored by Epworth Sleepiness Scale (ESS). The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Results The levels of MHT, 111, LAT, Al, RD1, M-AI, ESS and serum MDA were decreased in the three groups after treatment, the levels of LSaO2 , REM and serum SOD were increased in the three groups after treatment as compared with those before treatment (all P<0.0 5). Compared with the control group, the levels of MHT, 111, RD1, M-A1, ESS and serum MDA in low-dose GSPE group and high-dose GSPE group were decreased after treatment, the levels of LSa02 and REM were increased after treatment, and the changes were more significant in the high-dose GSPE group (all P <0. 05 ). There was no significant difference in LAT, Al and serum SOD between the three groups after treatment (all P >0.05). Conclusions GSPE adjuvant treatment can improve the sleep structure and sleep quality of OSAHS patients, and the mechanism may be the reduction of oxidative stress reaction. [ABSTRACT FROM AUTHOR]

Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red-victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin-1 (ET-1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension-induced arterial remodeling, which was not associated with blood pressure control. ET-1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension-induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti-arterial remodeling agent for patients with hypertensive vascular diseases. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the protective effect of grape seed proanthocyanidin extract (GSPE) on cadmium (Cd)-induced testicular apoptosis, endothelial nitric oxide synthases (eNOS) expression, and toxicity in rats. A total of 24 male Wistar rats were divided into four groups, namely, control, Cd (2.5 mg/kg), Cd + GSPE (100 mg/kg/day), and GSPE. Spermatogenesis and mean seminiferous tubule diameter were significantly decreased in the Cd groups. Furthermore, the GSPE-treated animals showed an improved histological appearance in the Cd group. The immunoreactivity of eNOS and the number of apoptotic cells were increased in Cd group. Our data indicate a significant reduction of terminal deoxynucleotide transferase-mediated 2′-deoxyuridine 5′-triphosphate nick end-labeling staining and a decrease in the expression of eNOS in the testes tissue of the Cd group treated with GSPE therapy. Therefore, our results suggest that GSPE acts as a potent protective agent against Cd-induced testicular toxicity in rats. [ABSTRACT FROM AUTHOR]

Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, -glutamyl cysteine synthetase (-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway. [ABSTRACT FROM AUTHOR]

The aim was to investigate the prevention of grape seed proanthocyanidin extract (GSPE) on the subchronic immune injury induced by aflatoxin B1 (AFB1) and the possible ameliorating effect of GSPE in mice. The subchronic AFB1-induced immune injury mice model was set up with the continuous administration of 100 μg/kg body weight (BW) AFB1 for six weeks by intragastric administration. Then, intervention with different doses (50 and 100 mg/kg BW) of GSPE was conducted on mice to analyze the changes of body weight, immune organ index, antioxidant capability of spleen, serum immunoglobulin content, and the expression levels of inflammatory cytokines. The prevention of GSPE on the immune injury induced by AFB1 was studied. The GSPE could relieve the AFB1-induced reduction of body weight gain and the atrophy of the immune organ. The malondialdehyde (MDA) level of the spleen in the AFB1 model group significantly increased, but levels of catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) significantly decreased. The GSPE could significantly inhibit the oxidative stress injury of the spleen induced by AFB1. AFB1 exposure could not significantly change the contents of IgA, IgG, or IgM. AFB1 significantly improved the expression of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and interferon (IFN-). Additionally, GSPE could decrease the expression of these four proinflammatory factors to different degrees and inhibit the inflammatory reaction of mice. The results suggest that GSPE alleviates AFB1-induced oxidative stress and significantly improves the immune injury of mice induced by AFB1. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of grape seed proanthocyanidin extract (GSPE) on indoxyl sulfate-induced Human Umbilical Vein Endothelial Cells (HUVECs) injuryin vitroand study its mechanism.Methods: HUVECs were incubated with indoxyl sulfate at concentrations in the range found in uremic patients. Then we determined the effect of indoxyl sulfate on endothelial phenotype, endothelial function, ROS (reactive oxygen species), cell apoptosis and mitochondrial function. In addition, we detected whether GSPE can suppress the injury of HUVECs induced by indoxyl sulfate and probe the mechanism underlying the protective effects of GSPE by analyzing mitochondrial dysfunction.Results: GSPE treatment significantly attenuated indoxyl sulfate-induced HVUECs injury in a dose- and time-dependent manner. GSPE-enhanced eNOS and VE-cadherin expression, inhibited intracellular ROS level and cell apoptosis, adjust mitochondrial membrane potential and reduced 8-hydroxy-desoxyguanosine (8-OHdG) level induced by indoxyl sulfate.Conclusion: These results suggest that GSPE prevents HUVECs from indoxyl sulfate-induced injury by ameliorating mitochondrial dysfunction and may be a promising agent for treating uremia toxin-induced injury. [ABSTRACT FROM AUTHOR]

To investigate whether grape seed proanthocyanidin extract (GSPE) antagonizes fluoride-induced oxidative injury by regulating iron metabolism, human embryo hepatic cells (L-02) were incubated with sodium fluoride (NaF, 80 mg/L) and/or GSPE (100 μmol/L) for 24 h. Results showed the glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) level of the NaF group were significantly lower than that of the control group ( P < 0.05), while malondialdehyde (MDA) content increased in the NaF group compared with the control group ( P < 0.05). Moreover, the indexes mentioned above showed opposite changes in the NaF + GSPE group. In addition, iron content significantly increased in the NaF group compared to the control group( P < 0.05) and significantly decreased in the NaF + GSPE group compared to the NaF group ( P < 0.05). Furthermore, hepcidin (coded by HAMP) messenger RNA (mRNA) expression significantly increased in the NaF group compared to the control group( P < 0.05) and significantly decreased in the NaF + GSPE group compared to the NaF group ( P < 0.05). Ferroportin 1 (coded by FPN1) mRNA expression significantly decreased in the NaF group compared to the control group ( P < 0.05) and significantly increased in the NaF + GSPE group compared to the NaF group ( P < 0.05). These results indicate that GSPE provides significant cellular protection against oxidative stress induced by excessive fluoride via the iron metabolism regulation. [ABSTRACT FROM AUTHOR]

Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S -transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusions GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity. [ABSTRACT FROM AUTHOR]

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg∙bw), medium (250 mg/kg∙bw) or high (500 mg/kg∙bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg∙bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]