Grape Seed Extract Exerts an Anti-Apoptotic Effect and Attenuates the Decrease in Striatal Tyrosine Hydroxylase in Rotenone-Treated Mice

Abstract

The potential neuroprotective effect of grape seed extract (GSE) was evaluated in the rotenoneinduced Parkinson's disease in mice. Rotenone was administered at the dose of 1.5 mg/kg subcutaneously (sc) three times per week for 2 weeks alone or in combination with GSE at doses of 13.5 and 27 mg/kg, sc, daily. The control group received the vehicle. The brain levels of the lipid peroxidation product malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite), and paraoxonase-1 (PON-1) were determined. Histopathology, caspase-9 immunohistochemistry in different brain regions, and tyrosine hydroxylase immunoreactivity (TH-ir) in the substantia nigra were performed. Behavioral testing included rearing activity, locomotor activity, and stair test paradigms. Results indicated significantly increased lipid peroxidation and nitric oxide contents along with a significant decrease in GSH level and marked inhibition of PON-1 activity in the striatum and in the rest of the brain tissue in rotenone-treated mice. Rotenone caused significant decreases in rearing and locomotor activities and impaired motor strength. Treatment with GSE at 27 mg/kg resulted in decreased MDA and nitric oxide by 22.8%/17.9% and 38.5%/45.5%, respectively, in the striatum and the rest of the brain. GSH was increased by 20.8% and 26%, while PON-1 activity increased by 204% and 142.9% after GSE treatment in the striatum and in the rest of the brain tissue, respectively, compared with the corresponding rotenone control values. GSE given at 27 mg/kg almost completely corrected the decrease in motor activity and motor strength caused by rotenone. Neuronal degeneration and the increase in caspase-9 expression caused by rotenone in different brain regions as well as the loss of substantia nigra TH-ir were markedly reduced by GSE. These data indicate that GSE was effective in improving brain oxidative stress and in preventing the behavioral deficits and neurodegeneration induced by rotenone in the mouse brain. It is suggested that GSE might be useful as an adjunctive treatment in patients with Parkinson's disease.

Grape-Leaf Extract Attenuates Alcohol-Induced Liver Injury via Interference with NF-κB Signaling Pathway

“…Another major component that associates all forms of liver injury is apoptosis, which could be triggered by both NF-κB/inflammatory cytokines (e.g., TNF-α) and by excessive intracellular ROS, leading to activation of caspases (e.g., caspase 3) and subsequent cell death. Interestingly, apoptosis causative factors are able not only to induce apoptosis, but also to simultaneously stimulate survival signals (e.g., survivin) against cell death [52,53], with an end result (cell death or survival) depending on the severity of the initial insult [54]. The EtOH (current study) caused an increased expression of both apoptotic (caspase-3) and antiapoptotic (survivin) markers, and those changes were alleviated by GLE, which correlated well with its hepatoprotective effects demonstrated in the current study.…”