title: S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase.
abstract: Diabetes mellitus (DM) is associated with learning, memory, and cognitive deficits. S-allyl cysteine (SAC) is the main organosulfur bioactive molecule in aged garlic extract with anti-diabetic, antioxidant, anti-inflammatory and nootropic property. This research was conducted to evaluate the efficacy of SAC on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats and to explore involvement of toll-like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-kappa B (NF-κB), and heme oxygenase 1 (HO-1) signaling cascade. Male Wistar rats were divided into control, diabetic, SAC-treated diabetic, and glibenclamide-treated diabetic (positive control) groups. SAC was administered at a dose of 150mg/kg for seven weeks. Treatment of diabetic rats with SAC lowered serum glucose, improved spatial recognition memory in Y maze, discrimination ratio in novel object recognition task, and restored step-through latency (STL) in passive avoidance paradigm. In addition, SAC reduced acetylcholinesterase activity, lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system including superoxide dismutase (SOD), catalase and reduced glutathione (GSH) in hippocampal lysate. Meanwhile, SAC lowered hippocampal NF-kB, TLR4, and TNFα and prevented reduction of Nrf2 and heme oxygenase-1 (HO-1) in diabetic rats. Taken together, chronic SAC treatment could ameliorate cognitive deficits in STZ-diabetic rats through modulation of Nrf2/NF-κB/TLR4/HO-1, and acetylcholinesterase and attenuation of associated oxidative stress and neuroinflammation.
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Tourandokht
authors.initials: T
authors.lastname: Baluchnejadmojarad
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: kiasalari@shahed.ac.ir.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kiasalari
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors.forename: Siamak
authors.initials: S
authors.lastname: Afshin-Majd
authors.affiliation: Department of Physiology, School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ghasemi
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: mroghani@shahed.ac.ir.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004192:Discrimination, Psychological / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; C065299:S-allylcysteine; D000110:Acetylcholinesterase; D003545:Cysteine
keywords: Cognition; Diabetes mellitus; Learning and memory; S-allyl cysteine; Streptozotocin