Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Shahed University, Tehran, Iran.
Eur J Pharmacol. 2017 Jan 5;794:69-76. doi: 10.1016/j.ejphar.2016.11.033. Epub 2016 Nov 22.
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.
糖尿病（DM）与学习、记忆和认知功能障碍有关。S-烯丙基半胱氨酸（SAC）是陈年大蒜提取物中的主要含硫生物活性分子，具有抗糖尿病、抗氧化、抗炎和促智作用。本研究旨在评估 SAC 对链脲佐菌素（STZ）-糖尿病大鼠学习和记忆障碍的缓解作用，并探讨其对 Toll 样受体 4（TLR4）、核因子（红细胞衍生 2）样 2（Nrf2）、核因子-κB（NF-κB）和血红素加氧酶 1（HO-1）信号级联的影响。雄性 Wistar 大鼠分为对照组、糖尿病组、SAC 治疗糖尿病组和格列本脲治疗糖尿病组（阳性对照组）。SAC 以 150mg/kg 的剂量给药 7 周。SAC 治疗糖尿病大鼠可降低血清葡萄糖水平，改善 Y 迷宫中的空间识别记忆、新物体识别任务中的辨别率，并恢复被动回避范式中的步移潜伏期（STL）。此外，SAC 降低了海马裂解物中的乙酰胆碱酯酶活性、脂质过氧化标志物丙二醛（MDA），并增强了抗氧化防御系统，包括超氧化物歧化酶（SOD）、过氧化氢酶和还原型谷胱甘肽（GSH）。同时，SAC 降低了糖尿病大鼠海马中的 NF-κB、TLR4 和 TNFα，并防止了 Nrf2 和血红素加氧酶-1（HO-1）的减少。综上所述，慢性 SAC 治疗可通过调节 Nrf2/NF-κB/TLR4/HO-1、乙酰胆碱酯酶以及减轻相关氧化应激和神经炎症来改善 STZ 糖尿病大鼠的认知功能障碍。
