Yaghoob Farbood1, Shahab Ghaderi2, Masome Rashno3, Seyed Esmaeil Khoshnam1, Layasadat Khorsandi4, Alireza Sarkaki1, Mohammad Rashno5. 1. Department of Physiology, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2. Department of Physiology, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: Ghaderi.shahab@yahoo.com. 3. Department of Physiology, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: Masome.rashno@yahoo.com. 4. Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 5. Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Abstract
AIMS: Hippocampal oxidative stress and apoptosis of CA1 neurons play significant roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The present study was aimed to elucidate the putative effects of sesamin, a major lignan of sesame seed, against DACD, and possible involvement of anti-oxidative and anti-apoptotic mechanisms. MAIN METHODS: Fifty adult male Wistar rats were randomly divided into control, control-sesamin (30 mg/kg/day), diabetic, diabetic-sesamin (30 mg/kg/day), and diabetic-insulin (6 IU/rat/day) groups. Diabetic rats were treated with sesamin (P.O.) or insulin (S.C.) for eight consecutive weeks. Cognitive performance was evaluated in a Morris Water Maze (MWM) test; in addition, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) concentrations were assayed in the hippocampus using assay kits. Moreover, hematoxylin-eosin (HE), TUNEL, and immunohistochemistry (IHC) stainings were conducted to evaluate histological changes, the apoptosis status and expression of pro- and anti-apoptotic proteins in the hippocampal CA1 neurons, respectively. KEY FINDINGS: The results showed that diabetes reduced the spatial cognitive ability in MWM, which was accompanied by decrease in SOD, CAT, and GPx activities and increase in MDA level in the hippocampus. Additionally, diabetes resulted in neuronal loss, enhanced apoptotic index, elevated the expression of pro-apoptotic Bax protein, and decreased the expression of anti-apoptotic Bcl-2 protein in the hippocampal CA1 neurons. Interestingly, sesamin treatment improved all the above-mentioned deficits of diabetes at a comparable level with insulin therapy. SIGNIFICANCE: The results suggest that sesamin could be a promising potential therapeutic agent against DACD, possibly through its intertwined anti-hyperglycemic, anti-oxidative, and anti-apoptotic properties.
AIMS: Hippocampal oxidative stress and apoptosis of CA1 neurons play significant roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The present study was aimed to elucidate the putative effects of sesamin, a major lignan of sesame seed, against DACD, and possible involvement of anti-oxidative and anti-apoptotic mechanisms. MAIN METHODS: Fifty adult male Wistar rats were randomly divided into control, control-sesamin (30 mg/kg/day), diabetic, diabetic-sesamin (30 mg/kg/day), and diabetic-insulin (6 IU/rat/day) groups. Diabeticrats were treated with sesamin (P.O.) or insulin (S.C.) for eight consecutive weeks. Cognitive performance was evaluated in a Morris Water Maze (MWM) test; in addition, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) concentrations were assayed in the hippocampus using assay kits. Moreover, hematoxylin-eosin (HE), TUNEL, and immunohistochemistry (IHC) stainings were conducted to evaluate histological changes, the apoptosis status and expression of pro- and anti-apoptotic proteins in the hippocampal CA1 neurons, respectively. KEY FINDINGS: The results showed that diabetes reduced the spatial cognitive ability in MWM, which was accompanied by decrease in SOD, CAT, and GPx activities and increase in MDA level in the hippocampus. Additionally, diabetes resulted in neuronal loss, enhanced apoptotic index, elevated the expression of pro-apoptotic Bax protein, and decreased the expression of anti-apoptotic Bcl-2 protein in the hippocampal CA1 neurons. Interestingly, sesamin treatment improved all the above-mentioned deficits of diabetes at a comparable level with insulin therapy. SIGNIFICANCE: The results suggest that sesamin could be a promising potential therapeutic agent against DACD, possibly through its intertwined anti-hyperglycemic, anti-oxidative, and anti-apoptotic properties.