Background: Silent information regulator 1 (SIRT1), a histone deacetylase, plays a protective role in ischemic brain injury. Previous studies have shown that magnolol has a beneficial effect on ischemic stroke; however, the role of SIRT1 in the protective effect of magnolol against cerebral ischemia has not been investigated.
Methods: We used a middle cerebral artery occlusion model of stroke in rats. Before stroke induction, the rats received intraperitoneal injections of magnolol with or without the SIRT1 inhibitor, EX527. Brain water content, neurological score, and infarct volume were measured. Moreover, the levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured. Western blot analysis was performed to detect Ac-FOXO1, SIRT1, bax, and Bcl-2 expression.
Results: Magnolol exerted a beneficial effect on cerebral ischemia, as indicated by reduced brain edema, decreased infarct volume, and improved neurological score. Magnolol had an anti-inflammatory effect mediated by a decrease in the expression of IL-1β and TNF-α in the brain tissue. Additionally, magnolol down-regulated bax and Ac-FOXO1 expression and up-regulated Bcl-2 and SIRT1 expression. This effect of magnolol was abolished by EX527 treatment.
Conclusion: In conclusion, our data clearly indicate that magnolol modulates brain injury caused by ischemic stroke by inhibiting inflammatory cytokines and apoptosis through SIRT1 activation.
Keywords: Apoptosis; Inflammation; Ischemic stroke; Magnolol; SIRT1.
Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.