Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xi'an, P.R. China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, P.R. China.
Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, P.R. China.
Phytomedicine. 2021 Jul;87:153577. doi: 10.1016/j.phymed.2021.153577. Epub 2021 Apr 18.
When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.
The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (HO)-induced injury in SH-SY5Y cells in vitro.
SH-SY5Y cells were simultaneously treated with AU and HO for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry.
The results showed that AU can significantly increase the HO-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that HO stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In HO-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways.
These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.
当大脑中的氧化还原平衡失调时，氧化应激会导致严重的损伤，导致神经元丧失，与神经退行性疾病一致。梓醇（AU）是一种环烯醚萜苷，是杜仲的活性成分之一，具有许多药理作用，如抗炎、抗肝纤维化和抗动脉粥样硬化。
本研究旨在评估 AU 对体外过氧化氢（HO）诱导的 SH-SY5Y 细胞氧化应激损伤的抑制作用。
SH-SY5Y 细胞同时用 AU 和 HO 处理 24 小时。通过 CCK-8 法测定细胞活力。此外，通过流式细胞术测定线粒体膜去极化、活性氧（ROS）生成和细胞凋亡。
结果表明，AU 能显著提高 HO 诱导的细胞活力和线粒体膜电位，降低 ROS 生成、丙二醛（MDA）含量，增加谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）活性。我们还发现，HO 刺激一氧化氮（NO）的产生，而 AU 通过抑制诱导型一氧化氮合酶（iNOS）蛋白表达可以减少 NO 的产生。在 HO 诱导的 SH-SY5Y 细胞中，AU 通过核因子 E2 相关因子 2/血红素加氧酶-1（Nrf2/HO-1）激活，抑制 p-NF-κB/NF-κB 表达和下调 MAPK 和 Bcl-2/Bax 途径，降低肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）含量和细胞凋亡。
这些结果表明，AU 通过 NF-κB、Nrf2/HO-1 和 MAPK 途径减少炎症和氧化应激。
