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bioRxiv · 10.1101/2024.09.13.612855

Preventive Effects of Pomegranate Seed Oil on Transient Middle Cerebral Artery Occlusion via the Keap1/Nrf2/NQO1 Pathway in the rats Cortex

Li, D.·Zhang, C.·Luo, Q.·Li, M.·Tian, M.·Jiao, H.·Xi, X.·Weng, Q.
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Abstract

Ischemic stroke remains a pressing challenge that needs to be solved. Energy metabolic failure is a critical factor contributing to mitochondrial dysfunction and oxidative stress in the pathogenesis of brain ischemia, leading to the generation of excessive reactive oxygen species. Pomegranate seed oil (PSO) exhibits antioxidant properties; however, its protective effects against cerebral ischemia/reperfusion injury and the underlying mechanisms remain unclear. In this study, a transient middle cerebral artery occlusion (tMCAO) rat model was employed to simulate cerebral ischemia/reperfusion injury. We investigated the mechanisms by which different concentrations of PSO modulate oxidative damage caused by cerebral ischemia/reperfusion injury through the Keap1/Nrf2/NQO1 pathway in cortex. SD male rats were randomly divided into four groups: Control, tMCAO+NaCl, tMCAO+LO (low concentration of PSO), tMCAO+MO (medium concentration of PSO), and tMCAO+HO (high concentration of PSO). Our findings suggest that low concentration of PSO exerts neuroprotective effects by activating Nrf2 and NQO1, thereby reducing oxidative stress. Furthermore, LO significantly improved neurological scores and reduced neuronal edema. Additionally, the results demonstrated an increase in superoxide dismutase (SOD) levels and a decrease in malondialdehyde (MDA) levels. In contrast, MO and HO exhibited suboptimal effects. To sum up, these results indicate that PSO activates neuroprotective pathways against oxidative stress following cerebral ischemia/reperfusion injury via the Keap1/Nrf2/NQO1 pathway, providing novel insights into potential preventive therapies for cerebral ischemia/reperfusion.

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Li, D., Zhang, C., Luo, Q., Li, M., Tian, M., Jiao, H., Xi, X., Weng, Q.. 2024-09-15. Preventive Effects of Pomegranate Seed Oil on Transient Middle Cerebral Artery Occlusion via the Keap1/Nrf2/NQO1 Pathway in the rats Cortex. https://doi.org/10.1101/2024.09.13.612855

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