Department of Anatomy, Basic Medical College, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Neurotox Res. 2021 Apr;39(2):349-358. doi: 10.1007/s12640-020-00284-z. Epub 2020 Sep 29.
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is currently incurable. Amyloid β protein (Aβ) deposition is the main pathogenesis of AD, and many studies have shown that Aβ accumulation is toxic to neurons, leading to the inflammatory reaction, neuronal apoptosis, and neurofibrillary tangles. Thus, reducing Aβ levels might be a potential therapeutic strategy for AD. Liquiritigenin (LG), a dihydroflavone monomer compound extracted from natural plant licorice, has a variety of biological activities such as antioxidant, anti-tumor, anti-inflammatory and anti-virus. However, the exact function of LG in the pathogenesis of AD is elusive. Here, we reported that LG could significantly attenuate neuronal apoptosis in Aβ-induced N2A cells and APP/PS1 transgenic mice. Our in vivo and in vitro studies revealed that LG could alleviate the inflammation response, reflected by the reduction of NLRP3 and cleaved caspase-1. Meanwhile, we also found that LG was able to shift M1 type microglia towards M2 type microglia in Aβ-induced BV2 cells and AD mice. Furthermore, LG could reduce the Aβ levels by decreasing APP processing and accelerating Aβ clearance in AD mice. More importantly, daily treatment of LG (30 mg/kg day) for 90 days dramatically ameliorated the spatial learning and memory of AD mice. Taken together, these results suggest that LG can reduce the Aβ levels by regulating the M1/M2 transformation of microglia, thereby reversing memory decline during AD development, suggesting that LG may be a potential therapeutic agent for treating AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，目前尚无治愈方法。β淀粉样蛋白（Aβ）沉积是 AD 的主要发病机制，许多研究表明 Aβ 积累对神经元有毒性，导致炎症反应、神经元凋亡和神经原纤维缠结。因此，降低 Aβ 水平可能是 AD 的一种潜在治疗策略。甘草素（LG）是从天然植物甘草中提取的二氢黄酮单体化合物，具有抗氧化、抗肿瘤、抗炎和抗病毒等多种生物学活性。然而，LG 在 AD 发病机制中的确切作用尚不清楚。在这里，我们报道 LG 可显著减轻 Aβ诱导的 N2A 细胞和 APP/PS1 转基因小鼠中的神经元凋亡。我们的体内和体外研究表明，LG 可以减轻炎症反应，表现为 NLRP3 和切割的 caspase-1 的减少。同时，我们还发现 LG 能够在 Aβ诱导的 BV2 细胞和 AD 小鼠中使 M1 型小胶质细胞向 M2 型小胶质细胞转化。此外，LG 可以通过减少 APP 处理和加速 AD 小鼠中 Aβ 的清除来降低 Aβ 水平。更重要的是，LG（30mg/kg·天）每天治疗 90 天可显著改善 AD 小鼠的空间学习和记忆。总之，这些结果表明，LG 可以通过调节小胶质细胞的 M1/M2 转化来降低 Aβ 水平，从而逆转 AD 发展过程中的记忆下降，表明 LG 可能是治疗 AD 的潜在治疗剂。
