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Am J Transl Res. 2019 Jan 15;11(1):199-209. eCollection 2019.

Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation.

Author information

1
Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, Shaanxi, China.
2
Department of Neurosurgery, The Affiliated Hospital of Shaanxi University of Chinese Medicine Xianyang 712020, Shaanxi, China.
3
Operation Room, Xianyang IRICO Hospital Xianyang 712000, Shaanxi, China.
4
Combination of Acupuncture and Medicine Innovation Research Center, Shaanxi University of Chinese Medicine Xianyang 712046, Shaanxi, China.
5
Department of Cerebropathy, The Affiliated Hospital of Shaanxi University of Chinese Medicine Xianyang 712020, Shaanxi, China.
6
College of Basic Medicine, The Shaanxi University of Chinese Medicine Xianyang 712046, Shaanxi, China.
7
Department of Administration, Xianyang IRICO Hospital Xianyang 712000, Shaanxi, China.

Abstract

Inflammation and oxidative stress are considered major factors in the pathogenesis of ischemic stroke. Increasing evidence has demonstrated that Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis, exhibits prominent anti-inflammatory and antioxidant activities. In this study, we investigated the anti-inflammatory and antioxidant effects of Sch A against cerebral ischemia/reperfusion (I/R) injury as well as the underlying molecular mechanisms. Sch A treatment significantly improved the neurological score and reduced infarct volume 24 h after reperfusion. It dose-dependently inhibited the expression of cyclooxygenase-2 and inducible nitric oxide synthase, reduced the release of pro-inflammatory cytokines (tumor necrosis factor-α interleukin [IL]-1β and IL-6), and increased anti-inflammatory cytokines (transforming growth factor-β and interleukin-10). Furthermore, it increased the activity of superoxide dismutase and catalase, decreased reactive oxygen species production and 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine levels. Transcription of nuclear factor erythroid 2-related factor 2 (Nrf2) and downstream genes (heme oxygenase-1 and NAD[P]H: quinone oxidoreductase 1) increased. Knockdown of Nrf2 by siRNA inhibited the neuroprotective effects of Sch A. In addition, Sch A increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) both in vivo and in vitro. Activation of the Nrf2 pathway as well as the protective effects of Sch A in an oxygen and glucose deprivation-induced injury model was abolished by AMPK knockdown. Our study indicates that Sch A protects against cerebral I/R injury by suppressing inflammation and oxidative stress, and that this effect is regulated by the AMPK/Nrf2 pathway.

KEYWORDS:

AMPK/Nrf2 pathway; Schizandrin A; inflammation; oxidative stress

PMID:
30787979
PMCID:
PMC6357305

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