College of Life Science, Henan Normal University, Xinxiang 453007, PR China.
Food Funct. 2018 Dec 13;9(12):6349-6359. doi: 10.1039/c8fo01497c.
(-)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechins, exhibits broad-spectrum health efficacy against mitochondrial damage after subarachnoid hemorrhage (SAH). The mechanisms, however, are largely unknown. Here, the ability of EGCG to rescue mitochondrial dysfunction and mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH models. EGCG blocked the cytosolic channel ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. As expected, EGCG ameliorated oxyhemoglobin (OxyHb)-induced impairment of mitochondrial dynamics by regulating the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the increases in fragmented mitochondria and the mtDNA copy number in the OxyHb group to almost the normal level after SAH. In addition, the normal autophagic flux induced by EGCG at both the initiation and formation stages regulated Atg5 and Beclin-1 after SAH for the timely elimination of damaged mitochondria. In the end, EGCG increased the neurological score by decreasing cell death through the cyt c-mediated intrinsic apoptotic pathway. The results revealed the mechanisms behind the neuroprotective effects of EGCG via inhibition of the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, the simultaneous inhibition and timely elimination of damaged mitochondria could determine the therapeutic effect of EGCG.
(-)-表没食子儿茶素没食子酸酯（EGCG）是茶儿茶素的主要生物活性成分，对蛛网膜下腔出血（SAH）后线粒体损伤具有广泛的健康功效。然而，其机制在很大程度上尚不清楚。本研究通过体外和体内 SAH 模型，研究了 EGCG 拯救线粒体功能障碍和线粒体动力学的能力，以抑制细胞死亡。EGCG 通过电压门控钙通道（VGCCs）阻断细胞质通道（[Ca2+]）i 流入，从而诱导线粒体功能障碍，包括线粒体膜电位去极化和活性氧（ROS）释放。不出所料，EGCG 通过调节 Drp1、Fis1、OPA1、Mfn1 和 Mfn2 的表达，改善了氧合血红蛋白（OxyHb）诱导的线粒体动力学损伤。结果，EGCG 使 OxyHb 组中碎片化线粒体的增加和 mtDNA 拷贝数恢复到 SAH 后的几乎正常水平。此外，EGCG 在起始和形成阶段诱导的正常自噬通量通过细胞色素 c 介导的内在凋亡途径调节 Atg5 和 Beclin-1，以实现对受损线粒体的及时清除。最后，EGCG 通过细胞色素 c 介导的内在凋亡途径减少细胞死亡来提高神经功能评分。结果揭示了 EGCG 通过抑制过载 [Ca2+]i 诱导的线粒体功能障碍和不平衡的线粒体融合和裂变循环来发挥神经保护作用的机制。因此，受损线粒体的同时抑制和及时消除可能决定 EGCG 的治疗效果。
