190. 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.

Giridharan VV[1], Thandavarayan RA[2], Arumugam S[3], Mizuno M[4], Nawa H[4], Suzuki K[5], Ko KM[6], Krishnamurthy P[2], Watanabe K[3], Konishi T[7,8]

[1] J.K.K. Nattraja College of Pharmacy, Komarapalayam, Tamil Nadu, India.
[2] Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas, United States of America.
[3] Department of Clinical Pharmacology, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata City, Japan.
[4] Division of Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
[5] Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
[6] Division of Life Science, Hong Kong University of Science and Technology, Clear water bay, Hong Kong.
[7] Basic studies on second generation functional foods, NUPALS, NUPALS Liaison R/D promotion division, Niigata, Japan. [8] Changchun University of Chinese Medicine, Changchun, RP China.

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-α, and DNA damage. Several proteins such as receptor for advanced glycation end products (RAGE), nuclear factor-κB, 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.