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

Amyloid beta (A beta)-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 A beta-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 A beta (1-40)-infused rats in step-through test. At the same time, Sch B attenuated A beta-induced increases in oxidative and nitrosative stresses, inflammatory markers such as inducible nitric oxide syntheses, cyclooxygenase-2, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha, and DNA damage. Several proteins such as receptor for advanced glycation end products (RAGE), nuclear factor-kappa B, mitogen-activated protein kinases, and apoptosis markers were over expressed in A beta-infused rats but were significantly inhibited by Sch B treatment. Furthermore, Sch B negatively modulated the A beta level with simultaneous up-regulation of HSP70 and beclin, autophagy markers in A beta-infused rats. The aforementioned effects of Sch B suggest its protective role against A beta-induced neurotoxicity through intervention in the negative cycle of RAGE-mediated A beta accumulation during AD patho-physiology.