Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, India.
Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, India.
Pharmacol Rep. 2018 Apr;70(2):372-377. doi: 10.1016/j.pharep.2017.09.006. Epub 2017 Sep 28.
Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) 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 Aβ overproduction via increased oxidative stress and AGEs. Trigonelline (TRG), a naturally occurring alkaloid has been reported to have neuroprotective and antidiabetic properties.
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.
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.
Present study highlights the neuroprotective role of TRG against d-gal induced amnesia due to the antioxidant, antiglycative and anticholinesterase properties.
阿尔茨海默病（AD）的特征是淀粉样β（Aβ）斑块、神经原纤维缠结（NFTs）和认知障碍。文献表明，由于氧化应激导致细胞毒性增加，晚期糖基化终产物（AGEs）在 AD 中起作用。半乳糖（d-gal）诱导的健忘症通过增加氧化应激和 AGEs 刺激 Aβ的过度产生。已报道瓜氨酸（TRG）作为一种天然存在的生物碱具有神经保护和抗糖尿病作用。
本研究评估了 TRG 对体外 AGEs 形成的保护作用。由于慢性给予 d-gal 会增加 AGEs，我们随后研究了 TRG（根据体重 50 和 100mg/kg）对 d-gal 诱导的健忘症的神经保护作用。小鼠皮下（sc）注射 d-gal（150mg/kg）6 周。进行 Morris 水迷宫（MWM）和 Y 迷宫行为评估，随后进行生化估计以推断可能的作用机制。
体外实验表明 TRG 阻止了早期和晚期 AGEs 的形成。慢性 d-gal 给药显着损害了 MWM 和 Y 迷宫中的认知表现，导致明显的氧化损伤，AGEs 水平升高，与假手术组相比，乙酰胆碱酯酶水平显着增加。与 d-gal 组相比，TRG（50 和 100mg/kg）治疗显着改善了认知表现，逆转了氧化损伤，降低了 AGE 水平，并显着降低了乙酰胆碱酯酶水平。
本研究强调了 TRG 对 d-gal 诱导的健忘症的神经保护作用，这归因于其抗氧化、抗糖化和抗乙酰胆碱酯酶特性。
