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Grape seed proanthocyanidin extract alleviates arsenic-induced lung damage through NF-?B signaling.

ABSTRACT: IMPACT STATEMENT:Arsenic-induced respiratory inflammatory damage is an important occupational hazard in many areas of the world, particularly in underdeveloped and developing countries. Effective treatments are lacking and expensive. Therefore, the aim of the study was to examine the anti-inflammatory effects of proanthocyanidin (PC) and the molecular mechanisms in vivo and in vitro. The present study showed that PC extracted from grape seed could attenuate the lung damage in a mouse model of arsenic poisoning. The effects were observed at the level of lung histology and inflammasome expression. This study suggests that a natural compound is effective in mitigating the toxic effects of arsenic in the lungs, providing an inexpensive and more readily accessible method for treating arsenic exposure in some parts of the world.

SUBMITTER: Hu Y

PROVIDER: S-EPMC6425101 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Grape seed proanthocyanidin extract alleviates arsenic-induced lung damage through NF-κB signaling.

Hu Yunhua Y Wei Meng M Niu Qiang Q Ma Rulin R Li Yu Y Wang Xianhua X Feng Gangling G Li Shugang S Pang Lijuan L

Experimental biology and medicine (Maywood, N.J.) 20190301 3

<h4>Impact statement</h4>Arsenic-induced respiratory inflammatory damage is an important occupational hazard in many areas of the world, particularly in underdeveloped and developing countries. Effective treatments are lacking and expensive. Therefore, the aim of the study was to examine the anti-inflammatory effects of proanthocyanidin (PC) and the molecular mechanisms in vivo and in vitro. The present study showed that PC extracted from grape seed could attenuate the lung damage in a mouse mod ...[more]

PMID: 30869553

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Grape Seed Proanthocyanidin Extract Alleviates AflatoxinB?-Induced Immunotoxicity and Oxidative Stress via Modulation of NF-?B and Nrf2 Signaling Pathways in Broilers.

Project description:Aflatoxin B? (AFB?) 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 AFB?-induced immunotoxicity and oxidative stress via NF-?B 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 + AFB? 1mg/kg contaminated corn (AFB?); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB? 1 mg/kg + GSPE 250 mg/kg (AFB? + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-?, IFN-?, IL-1?, IL-10, and IL-6 induced by AFB?. Similarly, GSPE + AFB? treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-?, IFN-?, IL-1?, and IL-6) in the splenic tissue compared to the AFB? treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of I?B? protein induced by AFB?. 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 AFB? group. Taken together, GSPE alleviates AFB?-induced immunotoxicity and oxidative damage by inhibiting the NF-?B 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 AFB?-induced immunotoxicity and oxidative damage.

| S-EPMC6356337 | biostudies-literature

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis.

Project description: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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Grape seed proanthocyanidin extract inhibits DNA and protein damage and labile iron, enzyme, and cancer cell activities.

Project description:Grape seed extract from (Vitis vinifera) (VGSE) is an excellent source of various polyphenols that exhibit highly potent antioxidant and disease prevention properties. Although numerous biological activities, with potential for improving human health, have been reported for VGSE, there is a lack of data relating to the health benefits of VGSE on DNA damage, protein damage, labile iron activity, and enzyme inhibitory effects. This investigation demonstrated, for the first time, that VGSE inhibits DNA and BSA damage and labile iron activity in-vitro. Moreover, VGSE also inhibited in-vitro activities of AChE, tyrosinase, and α-amylase. VGSE treatment significantly reduced viability of MCF-7, Hep-G2, Caco-2, and Huh-7 cells after 48-h treatments. The results obtained provide additional support for the purported health benefits of VGSE and reinforce its potential in disease prevention and therapy, especially in relation to cancer.

| S-EPMC9300616 | biostudies-literature

The Protective Effect of Grape-Seed Proanthocyanidin Extract on Oxidative Damage Induced by Zearalenone in Kunming Mice Liver.

Project description: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, γ-glutamyl cysteine synthetase (γ-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.

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Grape Seed Proanthocyanidin Alleviates Intestinal Inflammation Through Gut Microbiota-Bile Acid Crosstalk in Mice.

Project description:Regulation of gut microbiota and modulation of bile acid (BA) composition are potential strategies for the treatment of intestinal inflammation. This study aimed to investigate the effect of grape seed proanthocyanidin (GSP) on intestinal inflammation and to understand its mechanism. C57BL/6J male mice (7-8 weeks old) were used in experiments. Antibiotics were applied to deplete gut microbiota to evaluate the contribution of gut microbiota to the effect of dietary GSP. Intestinal-specific farnesoid X receptor (FXR) inhibitor was used to analyze the role of FXR signaling. In this study, GSP alleviated intestinal inflammation induced by LPS and altered the gut microbiota accompanied by increased abundance of hydroxysteroid dehydrogenase (HSD) producing microbes. GSP activated the intestinal FXR signaling pathway and increased gene expression of enzymes of the alternative BA synthetic pathway, which associated with elevated levels of chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) in liver and feces. However, gut microbiota depletion by antibiotics removed those effects of GSP on mice injected with LPS. In addition, the protective effect of GSP on mice challenged with LPS was weakened by the inhibition of intestinal FXR signaling. Further, the mixture of CDCA and LCA mirrored the effects of GSP in mice injected with LPS, which might verify the efficiency of CDCA and LCA on intestinal inflammation. Taken together, our results indicated that GSP exerted an intestinal protection role in the inflammation induced by LPS, and these effects were mediated by regulating gut microbiota-BA crosstalk.

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Grape Seed Proanthocyanidin Extract Prevents Ovarian Aging by Inhibiting Oxidative Stress in the Hens.

Project description:Oxidative stress is an important inducement in ovarian aging which results in fecundity decline in human and diverse animals. As a potent antioxidant, grape seed proanthocyanidin extract (GSPE) was investigated to ameliorate chicken ovarian aging in this study. Firstly, ovarian antioxidant capacity of hens at different ages (90, 150, 280, and 580 days old) was compared to elucidate its age-related changes. Subsequently, a D-gal-induced (2.5 mg/mL) aging ovarian model was established and the cultured ovarian tissues were treated with GSPE at 5 μg/mL for 72 h to evaluate the putative attenuating effects of GSPE on ovarian aging. Meanwhile, ovaries of D280 (young) and D580 (old) were treated with GSPE for 72 h in culture to verify the protective effects of GSPE on natural aging ovary. The results showed that GSPE could rescue the antioxidant capacity decline by increasing the antioxidase activities and their gene expression in either D-gal-induced or natural aging ovaries. Moreover, GSPE could maintain the homeostasis between cell proliferation and apoptosis in the D-gal-induced and natural aging ovaries, as well as alleviate D-gal-induced nucleus chromatin condensation in the ovarian granulosa cells. In conclusion, GSPE treatment can effectively prevent the ovarian aging process in hens by reducing oxidative stress.

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Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation.

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| S-EPMC7602819 | biostudies-literature

Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice.

Project description: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.

| S-EPMC7747856 | biostudies-literature

Intervention of Grape Seed Proanthocyanidin Extract on the Subchronic Immune Injury in Mice Induced by Aflatoxin B1.

Project description: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 ?g/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-P(X)), 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 1? (IL-1?), IL-6, tumor necrosis factor ? (TNF-?), 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.

| S-EPMC4848972 | biostudies-literature

Defining Conditions for Optimal Inhibition of Food Intake in Rats by a Grape-Seed Derived Proanthocyanidin Extract.

Project description:Food intake depends on homeostatic and non-homeostatic factors. In order to use grape seed proanthocyanidins (GSPE) as food intake limiting agents, it is important to define the key characteristics of their bioactivity within this complex function. We treated rats with acute and chronic treatments of GSPE at different doses to identify the importance of eating patterns and GSPE dose and the mechanistic aspects of GSPE. GSPE-induced food intake inhibition must be reproduced under non-stressful conditions and with a stable and synchronized feeding pattern. A minimum dose of around 350 mg GSPE/kg body weight (BW) is needed. GSPE components act by activating the Glucagon-like peptide-1 (GLP-1) receptor because their effect is blocked by Exendin 9-39. GSPE in turn acts on the hypothalamic center of food intake control probably because of increased GLP-1 production in the intestine. To conclude, GSPE inhibits food intake through GLP-1 signaling, but it needs to be dosed under optimal conditions to exert this effect.

| S-EPMC5084038 | biostudies-literature

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