Yu Zejun, Jin Wenwen, Cui Yajie, Ao Mingzhang, Liu Hao, Xu Hang, Yu Longjiang
Institute of Resource Biology and Biotechnology, Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Luoyu Road Wuhan 430074 China
Key Laboratory of Molecular Biophysics, Ministry of Education Wuhan 430074 China.
RSC Adv. 2019 Jul 26;9(40):23096-23108. doi: 10.1039/c9ra03268a. eCollection 2019 Jul 23.
Maca has attracted considerable attention owing to its neuroprotective effects and . Macamides, a series of nonpolar and long-chain fatty acid -benzylamides, are considered unique constituents in maca. This study investigated the protective effects of ethanol extracts of maca (EEM) and macamides on corticosterone-induced (CORT) neurotoxicity in rat pheochromocytoma (PC12) cells. CORT reduced cell viability and increased LDH release, intracellular ROS levels, and MMP decline rate, and induced mitochondrial apoptosis. However, pretreatment with EEM and macamides ameliorated CORT-induced neurotoxicity. EEM increased the cell viability and reduced the LDH release. M 18:1, M 18:2, and M 18:3 increased cell viability and reduced LDH release and intracellular ROS generation. M 18:2 and M 18:3 inhibited MMP reduction and reduced the Bax/Bcl-2 ratios. M 18:1 reduced the intracellular ROS without affecting other factors. Moreover, M 18:3 prevented CORT-induced mitochondrial apoptosis, restrained the expression levels of pro-apoptotic proteins, namely, Bax, cytochrome C, cleaved-caspase-3, and cleaved-PARP, and increased the expression levels of Bcl-2. In addition, M 18:3 increased Akt phosphorylation and the ability of M 18:3 to protect against CORT-induced cytotoxicity was remarkably reduced by LY294002, a PI3K phosphorylation inhibitor. M 18:3 also elevated the phosphorylation of CREB and activated the BDNF protein levels in CORT-induced PC12 cells. In conclusion, macamides, especially M 18:3, exert protective effects on CORT-induced PC12 cells. The cellular mechanism of M 18:3 against CORT-induced cytotoxicity may involve inhibition of mitochondrial apoptosis, and activation of Akt and CREB phosphorylation. Overall, macamides may potentially treat neuronal damage induced by CORT.
玛咖因其神经保护作用而备受关注。玛卡酰胺是一系列非极性长链脂肪酸 - 苄基酰胺，被认为是玛卡中的独特成分。本研究调查了玛咖乙醇提取物（EEM）和玛卡酰胺对大鼠嗜铬细胞瘤（PC12）细胞中皮质酮诱导（CORT）的神经毒性的保护作用。CORT降低了细胞活力，增加了乳酸脱氢酶（LDH）释放、细胞内活性氧（ROS）水平和线粒体膜电位（MMP）下降率，并诱导线粒体凋亡。然而，用EEM和玛卡酰胺预处理可改善CORT诱导的神经毒性。EEM提高了细胞活力并减少了LDH释放。M 18:1、M 18:2和M 18:3提高了细胞活力，减少了LDH释放和细胞内ROS生成。M 18:2和M 18:3抑制了MMP降低并降低了Bax/Bcl-2比率。M 18:1降低了细胞内ROS，而不影响其他因素。此外，M 18:3预防了CORT诱导的线粒体凋亡，抑制了促凋亡蛋白Bax、细胞色素C、裂解的半胱天冬酶-3和裂解的聚（ADP-核糖）聚合酶（PARP）的表达水平，并增加了Bcl-2的表达水平。此外，M 18:3增加了Akt磷酸化，而PI3K磷酸化抑制剂LY294002显著降低了M 18:3保护细胞免受CORT诱导的细胞毒性的能力。M 18:3还提高了CORT诱导的PC12细胞中CREB的磷酸化水平并激活了脑源性神经营养因子（BDNF）蛋白水平。总之，玛卡酰胺，尤其是M 18:3，对CORT诱导的PC12细胞具有保护作用。M 18:3对抗CORT诱导的细胞毒性的细胞机制可能涉及抑制线粒体凋亡以及激活Akt和CREB磷酸化。总体而言，玛卡酰胺可能潜在地治疗由CORT诱导的神经元损伤。
