Punicalagin ameliorates the elevation of plasma homocysteine, amyloid-β, TNF-α and apoptosis by advocating antioxidants and modulating apoptotic mediator proteins in brain

Abstract

The present study investigated the neuroprotective role of punicalagin, a major polyphenolic compound of pomegranate on methionine-induced brain injury. Hyperhomocysteinemia (HHcy) was induced in two months old male BALB c mice by methionine supplementation in drinking water (1 g/kg body weight) 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 homocysteine, amyloid-β and TNF-α. HHcy is associated with a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (PGx) and glutathione reductase (GR) and glutathione (GSH) levels in the brains of methionine-treated mice while these antioxidants are increased by punicalagin supplementation. The treatment with punicalagin significantly decreased oxidative stress as indicated by decreased malondialdehyde and protein carbonyl formation in the brain. Compared with methionine-treated animals, mice that 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 hyperhomocysteinemic 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. In conclusion, punicalagin protected from methionine-induced HHcy and brain damage with an ability to repress apoptosis by modulating apoptotic mediators and maintaining DNA integrity in the brain of mice.