title: DADS Analogues Ameliorated the Cognitive Impairments of Alzheimer-Like Rat Model Induced by Scopolamine.
abstract: The development of agents that affect two or more relevant targets has drawn considerable attention in treatment of AD. Diallyl disulfide (DADS), an active principle of garlic, has been reported to prevent APP processing by amyloidogenic pathway. Recently, we have reported a new series of DADS derivatives and our findings revealed that compound 7k and 7l could provide good templates for developing new multifunctional agents for AD treatment. Thus, the present study was constructed to investigate the neuroprotective effect of DADS analogues (7k and 7l) against Aβ-induced neurotoxicity in SH-SY5Y human neuroblastoma cells and in ameliorating the cognition deficit induced by scopolamine in rat model. The results indicated that compound 7k and 7l significantly inhibited Aβ1-42-induced neuronal cell death by inhibiting ROS generation. Moreover, they prevented apoptosis, in response to ROS, by restoring normal Bax/Bcl-2 ratio. Furthermore, it was observed that scopolamine-induced memory impairment was coupled by alterations in neurotransmitters, acetylcholinesterase activity and oxidative stress markers. Histological analysis revealed severe damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Administration of compounds 7k and 7l at 5 mg/kg significantly reversed scopolamine-induced behavioural, biochemical, neurochemical and histological changes in a manner comparable to standard donepezil. Together the present findings and previous studies indicate that compounds 7k and 7l have neuroprotective and cognition-enhancing effects, which makes them a promising multi-target candidate for addressing the complex nature of AD.
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India.
authors.forename: Apra
authors.initials: A
authors.lastname: Manral
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Meena
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Saini
authors.affiliation: Department of Histopathology, National Institute of Pathology, Indian Council of Medical Research, New Delhi, India.
authors.forename: Fouzia
authors.initials: F
authors.lastname: Siraj
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Shalini
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India. mtiwari07@gmail.com.
authors.forename: Manisha
authors.identifier: 0000-0001-8942-0578
authors.initials: M
authors.lastname: Tiwari
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000812:Anhydrides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004220:Disulfides / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012601:Scopolamine; D013343:Styrenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000812:Anhydrides; D004220:Disulfides; D018697:Nootropic Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013343:Styrenes; C075222:amyloid beta-protein (1-42); C000608970:bis(2-(3, 4-dimethoxy phenyl)ethenyl)dithioperoxyanhydride; C000621360:bis(2-(3-methoxy-4-hydroxyphenyl)ethenyl)dithioperoxy anhydride; D012601:Scopolamine
keywords: Alzheimer’s disease; Amyloid beta protein; Elevated plus maze; Histopathology; Passive avoidance test; SH-SY5Y cells; Scopolamine