School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Biomed Pharmacother. 2018 Jan;97:152-161. doi: 10.1016/j.biopha.2017.10.106. Epub 2017 Nov 6.
Oxidative stress has been proposed to contribute to DNA damage and is involved in many neurodegenerative diseases. It has been reported that Aralia elata (Miq.) Seem. (A. elata) exhibits an anti-oxidative effect but the mechanisms underlying this protective effect are still unclear. In this study, six known triterpene saponins were isolated from the buds of A. elata, a well-known medicinal and edible plant in Northeast China. Subsequently, the anti-oxidative effects of all six triterpene saponins were screened by HO-induced damage in human neuronblastoma SH-SY5Y cells. Compound 6, also known as Eclalbasaponin I (EcI), was the most potent. Furthermore, the mechanism by which EcI combats HO-induced oxidative stress was investigated. The data suggested that EcI could down-regulate apoptosis induction and the generation of reactive oxygen species (ROS) induced by 200μM HO in SH-SY5Y cells. Moreover, EcI increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxides (GSH-Px), reduced the levels of malondialdehyde (MDA) to restore the antioxidant defense system, and activated the nuclear factor E2-related factor (Nrf2)/heme oxygenase 1 (HO-1) pathway to combat oxidative stress. In addition, EcI also promoted autophagy during this process. Interestingly, the protective effect was remarkably reversed by autophagy inhibitors, bafilomycin A1 (Baf) or 3-Methyladenine (3-MA). These results demonstrate that autophagy is contribute to the protective effect of EcI. Collectively, our findings provide a new insight into the potential protective effect of EcI by focusing on the role of autophagy.
氧化应激被认为有助于 DNA 损伤，并与许多神经退行性疾病有关。据报道，辽东楤木（Miq.）（A. elata）表现出抗氧化作用，但这种保护作用的机制尚不清楚。在这项研究中，从中国东北著名的药用和食用植物辽东楤木的芽中分离出了六种已知的三萜皂苷。随后，通过人神经母细胞瘤 SH-SY5Y 细胞中 HO 诱导损伤筛选了所有六种三萜皂苷的抗氧化作用。化合物 6，也称为 Eclalbasaponin I（EcI），是最有效的。此外，还研究了 EcI 对抗 HO 诱导的氧化应激的机制。数据表明，EcI 可以下调凋亡诱导和 200μM HO 诱导的 SH-SY5Y 细胞中活性氧（ROS）的产生。此外，EcI 增加了超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）等抗氧化酶的活性，降低了丙二醛（MDA）的水平，以恢复抗氧化防御系统，并激活核因子 E2 相关因子（Nrf2）/血红素加氧酶 1（HO-1）通路以对抗氧化应激。此外，EcI 在此过程中还促进了自噬。有趣的是，自噬抑制剂巴弗霉素 A1（Baf）或 3-甲基腺嘌呤（3-MA）显著逆转了这种保护作用。这些结果表明自噬有助于 EcI 的保护作用。总之，我们的研究结果提供了一个新的视角，即通过关注自噬的作用，探讨了 EcI 的潜在保护作用。
