Department of Cell Biology College of Basic Medical Sciences, Dalian Medical University, Dalian, P.R. China.
Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China.
Cell Cycle. 2021 Apr;20(7):661-675. doi: 10.1080/15384101.2021.1889186. Epub 2021 Mar 18.
Neurodegenerative disorders, including spinal cord injury (SCI), result in oxidative stress-induced cell damage. Morroniside (MR), a major active ingredient of the Chinese herb Shan Zhu Yu, has been shown to ameliorate oxidative stress and inflammatory response. Our previous study also confirmed that morroniside protects SK-N-SH cell line (human neuroblastoma cells) against oxidative impairment. However, it remains unclear whether MR also plays a protective role for oligodendrocytes that are damaged following SCI. The present study investigated the protective effects of MR against hydrogen peroxide (HO)-induced cell death in OLN-93 cells. MR protected OLN-93 cells from HO-induced injury, attenuated HO-induced increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and blocked the reduction of mitochondrial membrane potential (MMP) induced by H2O2. MR enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD) and suppressed HO-induced downregulation of the antiapoptotic protein Bcl-2 and activation of the proapoptotic protein caspase-3. Finally, we found that LY294002, a specific inhibitor of the PI3K/Akt pathway, inhibited the protective effect of MR against HO-induced OLN-93 cell injury in the MTT and TUNEL assays. LY294002 also inhibited the expression of SOD and Bcl-2, and increased the expression of iNOS and c-caspase-3 induced by MR treatment. MR exerts protective effects against HO-induced OLN-93 cell injury through the PI3K/Akt signaling pathway-mediated antioxidative stress and antiapoptotic activities. MR may provide a potential strategy for SCI treatment or other related neurodegeneration.
神经退行性疾病，包括脊髓损伤（SCI），会导致氧化应激诱导的细胞损伤。莫诺苷（MR）是山茱萸这种中国草药的主要活性成分之一，已被证明可改善氧化应激和炎症反应。我们之前的研究还证实，莫诺苷可保护 SK-N-SH 细胞系（人神经母细胞瘤细胞）免受氧化损伤。然而，目前尚不清楚 MR 是否对 SCI 后受损的少突胶质细胞也具有保护作用。本研究旨在探讨 MR 对过氧化氢（HO）诱导的 OLN-93 细胞死亡的保护作用。结果表明，MR 可保护 OLN-93 细胞免受 HO 诱导的损伤，减轻 HO 诱导的活性氧（ROS）和丙二醛（MDA）水平升高，并阻断 H2O2 诱导的线粒体膜电位（MMP）降低。MR 增强了抗氧化酶超氧化物歧化酶（SOD）的活性，并抑制了 HO 诱导的抗凋亡蛋白 Bcl-2 下调和促凋亡蛋白 caspase-3 激活。最后，我们发现，PI3K/Akt 通路的特异性抑制剂 LY294002，可抑制 MR 在 MTT 和 TUNEL 检测中对 HO 诱导的 OLN-93 细胞损伤的保护作用。LY294002 还抑制了 SOD 和 Bcl-2 的表达，并增加了 MR 处理诱导的 iNOS 和 c-caspase-3 的表达。MR 通过 PI3K/Akt 信号通路介导的抗氧化应激和抗凋亡作用，对 HO 诱导的 OLN-93 细胞损伤发挥保护作用。MR 可能为 SCI 治疗或其他相关神经退行性疾病提供一种潜在的治疗策略。
