A phenolic amide (LyA) isolated from the fruits of Lycium barbarum protects against cerebral ischemia-reperfusion injury via PKCε/Nrf2/HO-1 pathway.

Abstract

Lyciumamide A (LyA), a dimer of phenolic amide isolated from the fruits of Lycium barbarum, has been confirmed to possess potent antioxidant activity. This study was aimed to investigate the neuroprotection and molecular mechanisms of LyA against cerebral ischemia/reperfusion (I/R) injury via improving antioxidant activity. The model of middle cerebral artery occlusion (MCAO) and SH-SY5Y cells induced by oxygen and glucose deprivation (OGD) were adopted to verify the neuroprotective effects and the potential pharmacology mechanisms of LyA in vivo and in vitro. In MCAO model, treatment with LyA significantly improved neurologic score, reduced infarct volume, and relieved oxidative stress injury at 48 h after reperfusion. Meanwhile, LyA markedly increased the transcription Nrf2 and HO-1 expressions in the ischemic cerebral cortex. In vitro results showed that LyA protected differentiated SH-SY5Y cells against OGD-induced injury. LyA significantly decreased the expression of caspase-3 and the Bax/Bcl-2 ratio. But knockdown of Nrf2 or HO-1 attenuated the protective effect of LyA. Similarly, knockdown of protein kinase Cε (PKCε) inhibited LyA-induced Nrf2/HO-1 activation, and abated its protective effects. In conclusion, this study firstly demonstrated that LyA protects against cerebral I/R injury, ameliorates oxidative damage and neuronal apoptosis, partly via activation of PKCε/Nrf2/HO-1 pathway.

• Authors: Kai Gao, Meiyou Liu, Yi Ding, Minna Yao, Yanrong Zhu, Jinyi Zhao, Lianghua Cheng, Juan Bai, Fan Wang, Jinyi Cao, Jiankang Li, Haifeng Tang, Yanyan Jia, Aidong Wen
• Journal: Aging (Aging (Albany NY)) Vol. 11 Issue 24 Pg. 12361-12374 (12 26 2019) ISSN: 1945-4589 [Electronic] United States
• PMID: 31881005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Phenols
• lyciumamide A
• Heme Oxygenase-1
• Protein Kinase C-epsilon

Topics

• Amides (chemistry, pharmacology)
• Animals
• Brain Ischemia (pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Fruit
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Lycium (chemistry)
• Male
• NF-E2-Related Factor 2 (genetics, metabolism)
• Neuroblastoma
• Neuroprotective Agents (pharmacology)
• Phenols (chemistry, pharmacology)
• Protein Kinase C-epsilon (genetics, metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)