title: Akebia Saponin D attenuates amyloid β-induced cognitive deficits and inflammatory response in rats: involvement of Akt/NF-κB pathway.
abstract: Neuroinflammatory responses caused by amyloid β(Aβ) play an important role in the pathogenesis of Alzheimer's disease (AD). Aβ is known to be directly responsible for the activation of glial cells and induction of apoptosis. Akebia Saponin D (ASD) is extracted from a traditional herbal medicine Dipsacus asper Wall, which has been shown to protect against ibotenic acid-induced cognitive deficits and cell death in rats. In this study, we investigated the in vivo protective effect of ASD on learning and memory impairment induced by bilateral intracerebroventricular injections of Aβ1-42 using Morris water and Y-maze task. Furthermore, the anti-inflammatory activity and neuroprotective effect of ASD was examined with methods of histochemistry and biochemistry. These data showed that oral gavage with ASD at doses of 30, 90 and 270 mg/kg for 4 weeks exerted an improved effect on cognitive impairment. Subsequently, the ASD inhibited the activation of glial cells and the expression of tumor necrosis factor (TNF)-α, interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) in rat brain. Moreover, ASD afforded beneficial actions on inhibitions of Akt and IκB kinase (IKK) phosphorylations, as well as nuclear factor κB (NF-κB) activation induced by Aβ1-42. These results suggest that ASD may be a potential agent for suppressing both Alzheimer's disease-related neuroinflammation and memory system dysfunction.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, 210009 Nanjing, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.forename: Lin-na
authors.initials: LN
authors.lastname: Wang
authors.forename: Qian-ming
authors.initials: QM
authors.lastname: Du
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Ran
authors.initials: R
authors.lastname: You
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Ling
authors.forename: Zhong-lin
authors.initials: ZL
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D052003:NF-kappa B p52 Subunit; D010446:Peptide Fragments; D012503:Saponins; C534004:akebia saponin D; C075222:amyloid beta-protein (1-42); D051058:Oncogene Protein v-akt