Research Paper|Volume 11, Issue 24|pp 12361—12374

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

Kai Gao¹, Meiyou Liu¹, Yi Ding¹, Minna Yao¹, Yanrong Zhu¹, Jinyi Zhao¹, Lianghua Cheng¹, Juan Bai¹, Fan Wang¹, Jinyi Cao¹, Jiankang Li¹, Haifeng Tang^1,², Yanyan Jia¹, Aidong Wen¹

¹Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
²Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China

* Equal contribution

Received: June 22, 2019Accepted: November 26, 2019Published: December 26, 2019

https://doi.org/10.18632/aging.102578

Copyright © 2019 Gao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.