Schisandrin B ameliorates ICV-infused amyloid β induced oxidative stress and neuronal dysfunction through inhibiting RAGE/NF-κB/MAPK and Up-regulating HSP/beclin expression

Academic Article

Abstract

  • © 2015 Bastin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Amyloid β (Aβ)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). Our previous studies have demonstrated that schisandrin B (Sch B), an antioxidant lignan from Schisandra chinensis, could protect mouse brain against scopolamine- and cisplatin-induced neuronal dysfunction. In the present study, we examined the protective effect of Sch B against intracerebroventricular (ICV)-infused Aβ-induced neuronal dysfunction in rat cortex and explored the potential mechanism of its action. Our results showed that 26 days co-administration of Sch B significantly improved the behavioral performance of Aβ (1-40)-infused rats in step-through test. At the same time, Sch B attenuated Aβ-induced increases in oxidative and nitrosative stresses, inflammatory markers such as inducible nitric oxide syntheses, cyclooxygenase-2, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor- ?, and DNA damage. Several proteins such as receptor for advanced glycation end products (RAGE), nuclear factor-?B, mitogen-activated protein kinases, and apoptosis markers were over expressed in Aβ-infused rats but were significantly inhibited by Sch B treatment. Furthermore, Sch B negatively modulated the Aβ level with simultaneous up-regulation of HSP70 and beclin, autophagy markers in Aβ-infused rats. The aforementioned effects of Sch B suggest its protective role against Aβ-induced neurotoxicity through intervention in the negative cycle of RAGE-mediated Aβ accumulation during AD patho-physiology.
  • Published In

  • PLoS ONE  Journal
  • Digital Object Identifier (doi)

    Author List

  • Giridharan VV; Thandavarayan RA; Arumugam S; Mizuno M; Nawa H; Suzuki K; Ko KM; Krishnamurthy P; Watanabe K; Konishi TD
  • Volume

  • 10
  • Issue

  • 11