Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats

Devi, S. Asha; Chandrasekar, B; Manjula, K.; Ishii, Naokata

doi:10.1016/j.exger.2011.08.006

Cited by 67 publications

(23 citation statements)

References 24 publications

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“…GSPE has potent antioxidant effects [23]–[28]. Studies have shown that GSPE have anti-atherosclerotic effects both in animals and human subjects, which has been closely correlated with its antioxidant potency [29].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

et al. 2012

PLoS ONE

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BackgroundAtherosclerosis is one of the major complications of type 2 diabetic patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 (GSPB2) has demonstrated protective effect against atherosclerosis, which is believed to be, at least in part, a result of its antioxidative effects. The aim of this study is to identify the target protein of GSPB2 responsible for the protective effect against atherosclerosis in patients with DM.Methods and ResultsGSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db mice. The results showed that expression of 557 proteins were either up- or down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins were normalized by GSPB2 to the levels comparable to those in control mice. Among the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 (MFG-E8) was found to be increased in serum level in T2DM patients; the serum level of MFG-E8 was positively correlated with carotid-femoral pulse wave velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly suppressed whereas exogenous recombinant MFG-E8 administration exacerbated atherogenesis the db/db mice. To gain more insights into the mechanism of action of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of ERK1/2.ConclusionOur data suggests that MFG-E8 plays an important role in atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a well-studied antioxidant, significantly inhibited the arterial wall changes favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in aorta and its serum level. Measuring MFG-E8 serum level could be a useful clinical surrogate prognosticating atherogenesis in DM patients.

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

et al. 2012

PLoS ONE

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“…It is notable that pancreatic beta cells are considered especially susceptible to attacks by oxidative stress because of the very low expression of antioxidant enzymes as compared to other tissues. GSPs were reported to possess a broad spectrum of pharmacological, medicinal and therapeutic properties against oxygen free radicals and oxidative stress [34-36]. So it is still possible that GSPs affect ER stress by preventing oxidative stress on diabetic pancreas.…”

Section: Discussionmentioning

confidence: 99%

Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress

et al. 2013

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BackgroundIt is increasingly being realized that failure of pancreatic beta cells to secrete enough insulin to adequately compensate for obesity and insulin resistance is the primary defects of type 2 diabetes mellitus (T2DM). Pancreatic beta cells possess a highly developed and active endoplasmic reticulum (ER), reflecting their role in folding, export and processing of newly synthesized insulin. ER stress-induced pancreatic beta-cell failure is a novel event in the pathogenesis of T2DM. Some studies with antioxidants indicated a beneficial impact on ER stress. Our previous study found that strong antioxidants, grape seed proanthocyanidins (GSPs), ameliorated ER stress to protect skeletal muscle from cell death in type 2 diabetic rats. The present study continued to investigate the effect of GSPs on beta-cell failure and ER stress in diabetic pancreas.MethodsMale Sprague–Dawley rats made type 2 diabetic with 2 injections of 25 mg/kg streptozotocin and 8 weeks of the high-carbohydrate/high-fat diet were fed a basal diet with or without GSPs administration for 16 weeks. Oral glucose tolerance, plasma glucose, serum insulin and the score of beta-cell function were measured. Morphological observation was performed by light and electron microscopic analyses. Islet cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Additionally, the level of insulin and the expression of ER stress markers in pancreatic islets were also studied using immunohistochemical staining.ResultsAfter 16 weeks treatment, the score of beta-cell function and the abnormal oral glucose tolerance of diabetic rats were partially reversed by GSPs treatment. The efficacious effect of GSPs was also manifested in the amelioration of pancreatic damage and ER dilatation by microscopic analyses. Moreover, GSPs treatment increased normal insulin content and decreased the number of apoptotic cells in diabetic islets. Importantly, GSPs treatment partially alleviated ER stress by decreasing some ER stress markers.ConclusionThese findings suggest that GSPs might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction and death in T2DM.

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“…In addition, GSPE has demonstrated a wide range of biological effects, including antioxidant (19,20), anti-inflammatory (21,22), anti-mutagenic (23), anti-carcinogenic (24), cardioprotective (25,26) and neuroprotective (27) activities in various experimental models; furthermore, it can effectively reduce ischemia/reperfusion injury (28,29). Moreover, it has been reported to enhance working memory, ameliorate symptoms of Alzheimer’s disease (30), and significantly improve cognitive performance across age groups (31). However, little is known about the potential neuroprotective efficacy of GSPE against pentylenetetrazole (PTZ)-induced seizures.…”

Section: Introductionmentioning

confidence: 99%

Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats

Zhen

Fang

et al. 2014

International Journal of Molecular Medicine

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Numerous studies have demonstrated the antioxidant effects of grape seed proanthocyanidin extract (GSPE). The generation of free radicals and the ensuing apoptosis may contribute to the pathogenesis of epilepsy; therefore, in the present study, we examined the effects of GSPE on cognitive impairment and neuronal damage induced by chronic seizures in rats. Seizures were induced by a daily intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ; 35 mg/kg/day, 36 days). Two other groups were treated with GSPE (100 or 200 mg/kg/day, orally) for 24 days and then for 36 days prior to each PTZ injection. After the final PTZ injection, hippocampus-dependent spatial learning was assessed using the Morris water maze (MWM). The rats were then sacrificed for the measurement of hippocampal malondialdehyde (MDA, a measure of lipid peroxidation) and glutathione (GSH, a measure of endogenous antioxidant capacity) levels, and for the expression of pro-apoptotic factors [cytochrome c (Cyt c), caspase-9 and caspase-3]. The mitochondrial generation of reactive oxygen species (ROS), degree of mitochondrial swelling, neuronal damage and mitochondrial ultrastructure were also examined. Performance in the MWM was markedly impaired by PTZ-induced seizures, as evidenced by longer escape latencies during training and fewer platform crossings during the probe trial. This cognitive decline was accompanied by oxidative stress (MDA accumulation, ROS generation, reduced GSH activity), an increased expression of pro-apoptotic proteins, as well as damage to CA1 pyramidal neurons and the mitochondria. Pre-treatment with GSPE dose-dependently reversed PTZ-induced impaired performance in the MWM, oxidative stress, mitochondrial ROS generation, the expression of pro-apoptotic proteins and neuronal and mitochondrial damage. Thus, GSPE may reverse the hippocampal dysfunction induced by chronic seizures, by reducing oxidative stress and preserving mitochondrial function.

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Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats

Cited by 67 publications

References 24 publications

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress

Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats

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