Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Abstract

Summary Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-B p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-B p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-B p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-B p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-B p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-B pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats

“…Xu et al (2008) reported that oral administration of grape seed proanthocyanidin extracts decreased NF-kB p65 expression in the hippocampus of diabetic rats and reduced the negative structural changes associated with it. Lu et al (2010) found in a similar study that these grape seed proanthocyanidin-related positive effects were also seen in the cerebral cortices of STZ-induced diabetic rats. Grape seed proanthocyanidin extract have shown to protect human lens epithelial cells from H₂O₂-induced oxidative stress via reducing NF-кB and MAPK protein expression (Jia et al,2011).…”

“…However, it has also been alleged that it has limited effects in this context (Belviranli et al, 2012). Besides some of its' positive effects on the hippocampus (Xu et al, 2008) and cerebral cortex (Lu et al, 2010) of STZ-induced diabetic rats, we have not encountered any study about its' effects on diabetes-related cerebral neurodegeneration. Yet, it has been argued in recent years that it has neuroprotective effects in many individual diseases.…”

“…Grape seed extract (GSE) is another powerful free radical scavenger (Balu et al, 2006;Devi et al, 2006;Lu et al, 2010). Grape seeds contain flavonoids (catechin, epicatechin, procyanidins and anthocyanins) and…”

Grape Seed Procyanidin B2 Inhibits Human Aortic Smooth Muscle Cell Proliferation and Migration Induced by Advanced Glycation End Products

“…37,38) A GSPE treatment has decreased the aortic pulse wave velocity and aortic medial thickness by reducing the expression of AGE and RAGE in diabetic aortas. 39) GSPE has also demonstrated protective effects against nephropathy, 32) retinopathy, 31) and damage to peripheral nerves 33) and the cerebral cortex 40) in STZ-induced diabetic rats. We found in this present study that HASMCs stimulated with AGEs had a higher migration cell number and increased proliferation when compared with unstimulated HASMCs in a dosedependent manner.…”

Encefalopatia Diabética E Depressão: Dano Oxidativo No Cérebro

“…O paeonol mostrou atenuar o estresse oxidativo na encefalopatia diabética em ratos STZ, impedindo o prejuízo cognitivo, promovendo a diminuição na expressão do RAGE e do NF-κB no hipocampo e córtex, reduzindo o acúmulo de AGEs, o que pode estar relacionado com a inibição da via AGEs/RAGE/NF-κB envolvida com as complicações crônicas do diabetes 80 . Como já discutido por Lu et al 81 , a via AGEs/RAGE/NF-κB, crítica para o estresse oxidativo, está envolvida com a patogênese da encefalopatia diabética. Logo, os antioxidantes podem trazer benefícios para a saúde do cérebro, e sugere-se como potencial alvo terapêutico as proantocianidinas extraídas da semente da uva, cujas propriedades parecem modular vias redox sensíveis.…”