Basic Integrative Traditional Chinese & Western Medicine, Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi, Heilongjiang People's Republic of China.
Neuroreport. 2021 Feb 3;32(3):259-267. doi: 10.1097/WNR.0000000000001583.
For Alzheimer's disease (AD), there is still no effective treatment strategy. Pinoresinol diglucoside (PDG) is one of the major lignans isolated from Eucommia ulmoides. It is endowed with multiple pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. In this study, we investigated the potential neuroprotective functions of PDG in AD. Mice model with AD was established adopting stereotactic hippocampal injection of Aβ1-42 (410 pmol/mouse), and 3 days later, mice were administrated with 5 and 10 mg/kg PDG by intragastric administration every day for 3 weeks. Morris water maze and Y-maze tests demonstrated that PDG treatment could markedly reverse Aβ1-42-induced memory impairment in mice. It is found that PDG restrained the release of proinflammatory cytokines (tumor necrosis factor α and interleukin 1β), reactive oxygen species and malondialdehyde, and promoted the activity of the antioxidant enzyme (superoxide dismutase and catalase) by quantitative real-time-PCR, colorimetric method and ELISA assay. Western blot assay results have shown that PDG could also upregulate the ratio of Bcl-2/Bax and downregulate cytochrome c and cleaved caspase-3 expressions, thereby inhibiting neuronal apoptosis. Furthermore, PDG also significantly reduced the expression of Toll-like receptor 4 (TLR4) and the activation of nuclear factor-κB (NF-κB) p65, and promoted nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expressions. In conclusion, PDG can attenuate neuroinflammation, neuronal apoptosis and oxidative stress through the TLR4/NF-κB and Nrf2/HO-1 pathways, and ameliorate memory dysfunction induced by Aβ1-42 in mice.
对于阿尔茨海默病（AD），目前仍然没有有效的治疗策略。松脂素二葡萄糖苷（PDG）是从杜仲中分离得到的主要木脂素之一。它具有多种药理活性，包括抗炎、抗氧化和抗癌活性。在这项研究中，我们研究了 PDG 在 AD 中的潜在神经保护作用。采用立体定向海马注射 Aβ1-42（410 pmol/只）建立 AD 小鼠模型，3 天后，每天通过灌胃给予 5 和 10 mg/kg PDG，连续 3 周。Morris 水迷宫和 Y 迷宫测试表明，PDG 处理可显著逆转 Aβ1-42 诱导的小鼠记忆障碍。结果发现，PDG 通过定量实时 PCR、比色法和 ELISA 测定抑制促炎细胞因子（肿瘤坏死因子-α和白细胞介素 1β）、活性氧和丙二醛的释放，促进抗氧化酶（超氧化物歧化酶和过氧化氢酶）的活性。Western blot 检测结果表明，PDG 还可以上调 Bcl-2/Bax 比值，下调细胞色素 c 和裂解 caspase-3 的表达，从而抑制神经元凋亡。此外，PDG 还显著降低 Toll 样受体 4（TLR4）的表达和核因子-κB（NF-κB）p65 的激活，并促进核因子 E2 相关因子 2（Nrf2）和血红素加氧酶 1（HO-1）的表达。综上所述，PDG 通过 TLR4/NF-κB 和 Nrf2/HO-1 通路减轻神经炎症、神经元凋亡和氧化应激，改善 Aβ1-42 诱导的小鼠记忆功能障碍。
