Morroniside protects OLN-93 cells against H2O2-induced injury through the PI3K/Akt pathway-mediated antioxidative stress and antiapoptotic activities
Morroniside protects OLN-93 cells against H2O2-induced injury through the PI3K/Akt pathway-mediated antioxidative stress and antiapoptotic activities
复制标题
Morroniside 通过 PI3K/Akt 通路介导的抗氧化应激和抗凋亡活性保护 OLN-93 细胞免受 H(2)O(2) 诱导的损伤。
DOI：
10.1080/15384101.2021.1889186
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发表时间：
2021-03-19
期刊：
影响因子：
4.3
通讯作者：
Hu, Jianguo
中科院分区：
文献类型：
--
作者：
Li, Fengzhi;Song, Xue;Hu, Jianguo
神经退行性疾病，包括脊髓损伤（SCI），导致氧化应激诱导的细胞损伤。莫诺苷（MR）是中药山茱萸的主要活性成分，已被证明可以改善氧化应激和炎症反应。我们以前的研究也证实了莫诺苷保护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是否也对SCI后受损的少突胶质细胞起保护作用。本研究探讨了MR对过氧化氢（H2 O2）诱导的OLN-93细胞死亡的保护作用。MR对H2 O2诱导的OLN-93细胞损伤具有保护作用，能抑制H2 O2诱导的细胞内活性氧（ROS）和丙二醛（MDA）水平的升高，并能阻断H2 O2诱导的线粒体膜电位（MMP）的降低。MR增强了抗氧化酶超氧化物歧化酶（SOD）的活性，抑制H2 O2诱导的抗凋亡蛋白Bcl-2下调和促凋亡蛋白caspase-3的激活。最后，我们发现，LY 294002，一个特异性的PI 3 K/Akt通路的抑制剂，抑制MR对H2 O2诱导的OLN-93细胞损伤的保护作用在MTT和TUNEL法。LY 294002还能抑制MR诱导的SOD和Bcl-2的表达，增加iNOS和c-caspase-3的表达。MR通过PI 3 K/Akt信号通路介导的抗氧化应激和抗凋亡活性对H2 O2诱导的OLN-93细胞损伤发挥保护作用。MR可能为SCI或其他相关神经退行性变的治疗提供一种潜在的策略。
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 (H2O2)-induced cell death in OLN-93 cells. MR protected OLN-93 cells from H2O2-induced injury, attenuated H2O2-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 H2O2-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 H2O2-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 H2O2-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.