Park Euteum, Chun Hong Sung
Department of Biomedical Science, Chosun University.
Biol Pharm Bull. 2017 Aug 1;40(8):1275-1281. doi: 10.1248/bpb.b17-00160. Epub 2017 May 20.
Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.
姜黄素是姜黄中的一种生物活性成分，已被证明具有抗氧化、抗炎、抗癌、保肝和神经保护作用，但姜黄素对锰（Mn）介导的神经毒性的影响尚未得到研究。本研究考察了姜黄素对Mn诱导的BV-2小胶质细胞毒性的保护作用。姜黄素（0.1 - 10 μM）呈剂量依赖性地预防了Mn（250 μM）诱导的细胞死亡。Mn诱导的线粒体相关凋亡特征，如半胱天冬酶-3和-9的激活、细胞色素c的释放、Bax增加和Bcl-2减少，均被姜黄素显著抑制。此外，姜黄素显著增加细胞内谷胱甘肽（GSH）含量，并适度增强超氧化物歧化酶（SOD）活性，而这两者在Mn处理后均降低。姜黄素预处理有效抑制了Mn诱导的丙二醛（MDA）、总活性氧（ROS）的上调。此外，姜黄素显著抑制了Mn诱导的线粒体膜电位（MMP）丧失。此外，姜黄素能够诱导血红素加氧酶（HO）-1的表达。HO-1抑制剂（SnPP）部分逆转了姜黄素介导的对ROS的抑制、半胱天冬酶的下调、MMP的恢复以及细胞活力的恢复。这些结果首次表明，姜黄素可通过诱导HO-1以及调节氧化应激、线粒体功能障碍和凋亡事件来预防Mn诱导的小胶质细胞死亡。
