الفهرس 
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Abstract
Brain injury is associated with increased levels of homocysteine (Hcy), oxidative stress and deposition of amyloid-β (Aβ). The present study aimed to investigate the neuroprotective role of punicalagin, the major polyphenolic compound of pomegranate on methionine-induced brain injury. Hyperhomocysteinemia (HHcy) was induced in male mice by methionine supplement (1g/kg via drinking water) for 30 days. Punicalagin (1 mg/kg) was injected i.p every other day concurrently with methionine. Punicalagin significantly prevented the rise in the levels of Hcy, Aβ and TNF-α. HHcy is associated with a decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and glutathione levels in the brains of methionine-treated mice while these antioxidants are increased by punicalagin treatment in methionine-punicalagin treated group. Furthermore, treatment with punicalagin significantly decreased oxidative stress as indicated by decreased malondialdehyde and protein carbonyl concentrations in the brain. Compared with methionine treated animals that exhibited HHcy, mice treated with methionine and punicalagin remarkably displayed less apoptosis, indicated by the lower level of proapoptotic protein (Bax, caspases- 3, 9 and p53) and higher levels of antiapoptotic Bcl-2 protein than those in HHcy mice. The potent bioactivity of punicalagin extends to protect neuronal DNA as evidenced by the inhibition of the increase of comet parameters compared to the methionine-treated mice. The histopathological investigation reinforced the neuroprotective effect of punicalagin. In conclusion, punicalagin exhibited a neuroprotective effect evidenced by its ability to decrease Hcy, Aβ and TNF-α with repressing apoptosis by modulating apoptotic mediators, p53 and maintaining DNA integrity in the brain of mice.