期刊
PHARMACOLOGICAL REPORTS
卷 70, 期 2, 页码 372-377出版社
SPRINGER HEIDELBERG
DOI: 10.1016/j.pharep.2017.09.006
关键词
Alzheimer's disease; Advanced glycation end products; D-galactose; Oxidative stress; Trigonelline
资金
- University Grants Commission (UGC), New Delhi, India
Background: Alzheimer's disease (AD) is characterized by amyloid beta (A beta) plaques, neurofibrillary tangles (NFTs) and cognitive impairment. Literature cites the role of advanced glycation end products (AGEs) in AD due to increased cytotoxicity via oxidative stress. D-galactose (D-gal) induced amnesia stimulates Ab overproduction via increased oxidative stress and AGEs. Trigonelline (TRG), a naturally occurring alkaloid has been reported to have neuroprotective and antidiabetic properties. Methods: Present study assessed the protective effect of TRG against in vitro AGEs formation. Since chronic administration of D-gal increases AGEs, we subsequently investigated the neuroprotective role of TRG (50 and 100 mg/kg as per body weight) against D-gal induced amnesia. Mice were subcutaneously (sc) injected with D-gal (150 mg/kg) for 6 weeks. Behavioral assessments in Morris water maze (MWM) and Y-maze were performed, followed by biochemical estimations to deduce the probable mechanism of action. Results: In vitro experiments demonstrated that TRG stalled early and late AGEs formation. Chronic D-gal administration significantly impaired cognitive performance in MWM and Y maze, caused marked oxidative damage, elevated the AGEs levels and significantly increased the acetylcholinesterase levels as compared to sham group. TRG (50 and 100 mg/kg) treatment significantly ameliorated cognitive performance, reversed the oxidative damage, decreased AGE levels and caused significant decline in acetylcholine esterase levels as compared to D-gal group. Conclusion: Present study highlights the neuroprotective role of TRG against D-gal induced amnesia due to the antioxidant, antiglycative and anticholinesterase properties. (C) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o. o. All rights reserved.
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