Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.
Haemato-oncology/Systems Medicine Group, Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, MVLS, University of Glasgow, UK.
Oxid Med Cell Longev. 2021 Apr 16;2021:6635552. doi: 10.1155/2021/6635552. eCollection 2021.
The study was aimed at analyzing the protective effects of gintonin in an amyloid beta- (A-) induced Alzheimer's disease (AD) mouse model. For the development of the A-induced AD mouse model, the amyloid- (A ) peptide was stereotaxically injected into the brains of mice. Subsequently, gintonin was administered at a dose of 100 mg/kg/day/per oral (p.o) for four weeks daily, and its effects were evaluated by using western blotting, fluorescence analysis of brain sections, biochemical tests, and memory-related behavioral evaluations. To elucidate the effects of gintonin at the mechanistic level, the activation of endogenous antioxidant mechanisms, as well as the activation of astrocytes, microglia, and proinflammatory mediators such as nuclear factor erythroid 2-related factor 2 (NRF-2) and heme oxygenase-1 (HO-1), was evaluated. In addition, microglial cells (BV-2 cells) were used to analyze the effects of gintonin on microglial activation and signaling mechanisms. Collectively, the results suggested that gintonin reduced elevated oxidative stress by improving the expression of NRF-2 and HO-1 and thereby reducing the generation of reactive oxygen species (ROS) and lipid peroxidation (LPO). Moreover, gintonin significantly suppressed activated microglial cells and inflammatory mediators in the brains of A-injected mice. Our findings also indicated improved synaptic and memory functions in the brains of A-injected mice after treatment with gintonin. These results suggest that gintonin may be effective for relieving AD symptoms by regulating oxidative stress and inflammatory processes in a mouse model of AD. Collectively, the findings of this preclinical study highlight and endorse the potential, multitargeted protective effects of gintonin against AD-associated oxidative damage, neuroinflammation, cognitive impairment, and neurodegeneration.
本研究旨在分析金藤素在淀粉样蛋白β（Aβ）诱导的阿尔茨海默病（AD）小鼠模型中的保护作用。为了开发 Aβ诱导的 AD 小鼠模型，将淀粉样蛋白-（Aβ）肽立体定向注射到小鼠大脑中。随后，每天以 100mg/kg/天/口服（p.o）的剂量给予金藤素，连续 4 周，并通过 Western blot、脑切片荧光分析、生化测试和与记忆相关的行为评估来评估其效果。为了阐明金藤素的作用机制，评估了内源性抗氧化机制的激活，以及星形胶质细胞、小胶质细胞和促炎介质（如核因子红细胞 2 相关因子 2（NRF-2）和血红素加氧酶-1（HO-1））的激活。此外，还使用小胶质细胞（BV-2 细胞）来分析金藤素对小胶质细胞激活和信号转导机制的影响。总的来说，结果表明金藤素通过改善 NRF-2 和 HO-1 的表达来减轻氧化应激的升高，从而减少活性氧（ROS）和脂质过氧化（LPO）的产生。此外，金藤素显著抑制了 Aβ 注射小鼠大脑中活化的小胶质细胞和炎症介质。我们的研究结果还表明，金藤素治疗后可改善 Aβ 注射小鼠大脑中的突触和记忆功能。这些结果表明，金藤素可能通过调节 AD 小鼠模型中的氧化应激和炎症过程，对 AD 症状具有治疗作用。总的来说，这项临床前研究的结果强调了金藤素针对 AD 相关氧化损伤、神经炎症、认知障碍和神经退行性变的潜在多靶点保护作用。
