title: 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.
abstract: 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.
authors.affiliation: J.K.K. Nattraja College of Pharmacy, Komarapalayam, Tamil Nadu, India.
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata City, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Division of Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Division of Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
authors.affiliation: Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Section of Biochemistry and Cell biology, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Kam M
authors.initials: KM
authors.lastname: Ko
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata City, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Basic studies on second generation functional foods, NUPALS, NUPALS Liaison R/D promotion division, Niigata, Japan, Changchun University of Chinese Medicine, Changchun, RP China.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Konishi
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects; D000071186:Beclin-1; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D057967:Infusions, Intraventricular; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D034242:Cyclooctanes; D006360:Heat-Shock Proteins; D017705:Lignans; D016328:NF-kappa B; D011083:Polycyclic Compounds; D000067759:Receptor for Advanced Glycation End Products; C015499:schizandrin B; D020928:Mitogen-Activated Protein Kinases