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

Abstract

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.

Recovery of Chickens Affected with Tibial Dyschondroplasia by Application of Grape Seed Extract through Downregulating CA2 Gene and Enhancing Liver Functions

“…Grape seed proanthocyanidin extract (GSE) is extracted from grape seeds which contained favorable amounts of polymerized oligomers, polyphenolic flavonoids and oligomeric proanthocyanidins. Chinese used traditional medicines and GSE for the betterment of their fitness and animal health (Zhen et al, 2014). GSE played an important role in promoting anti-mutagenic (Sharma and Katiyar 2010), myocardial protecting (Demirkaya et al, 2009) and neurons protecting (Ahn et al, 2011) ability in various experimental trials.…”

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

“…Proanthocyanidin, a class of polyphenols with strong antioxidant properties commonly found in a variety of plants, have been reported to exert cell protective effects by reducing mitochondria damage and inhibiting cell apoptosis (Gao et al, 2014; Lu et al, 2015; Zhen et al, 2014). Grape seed proanthocyanidin extract (GSPE), an extract from grape seed, contains phenolic hydroxyl groups, which are well-known antioxidants (Ding et al, 2013; Mansouri et al, 2011), safe and well tolerated in humans (Sano, in press).…”

“…Previous studies reported that GSPE exerts anti-inflammatory (Park et al, 2012; Zhou et al, 2011), anti-carcinogenic (Uchino et al, 2010), anti-mutagenic (Sharma & Katiyar, 2010), and anti-ischemia/reperfusion injury (Song et al, 2012; Wei et al, 2012) effects, as well as cardioprotective (Bagchi et al, 2003; Demirkaya et al, 2009) and neuroprotective (Ahn et al, 2011) benefits. Proanthocyanidin also contains catechin, a flavanol capable of crossing the blood–brain barrier more easily than other natural antioxidants (Zhen et al, 2014), such as quercetin (Shen et al, 2013) and curcumin (Ahmad, 2013). However, the role of GSPE on lymphocyte apoptosis via its anti-oxidative property is poorly defined.…”

Üzüm Çekirdeği Ekstraktının Domuz Barsak Epitel Hücreleri Üzerine Oksidatif ve Proliferatif Etkileri

“…In this study, the contribution of GSE to the TAOC at low and medium levels (1 and 10 μg/mL, respectively) was moderate in unstressed or stressed IPEC1, but GSH was increased at 10 μg GSE/mL in unstressed cells, as well as at 1 and 10 μg/mL in the stressed cells. These results may represent the first direct evidence that a certain level of GSE can elevate the GSH contents in intestinal epithelial cells, although a few related studies have reported that dietary supplementation with GSE promotes an increase in GSH in the rat liver, the hippocampus and human serum [12,13] . Evidence indicates that some compositions of GSE (such as Quercetin, Epicatechin and Epicatechingallate) have the ability to stimulate GRed and γ-GCS activity, which act as the rate-limiting and key enzymes, respectively, in two major processes of GSH synthesis [14] , suggesting that GSE accelerated the synthesis of GSH.…”