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Evaluation of the neuroprotective effect of EGCG: a potential mechanism of mitochondrial dysfunction and mitochondrial dynamics after subarachnoid hemorrhage

Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechin, exhibited a broader spectrum health efficacy against mitochondrial damageafter subarachnoid hemorrhage (SAH), the mechanisms, however, are largely uncovered. Here, the ability of EGCG to rescue mitochondrial dysfunctionand mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH model. EGCG blocked cytosolic channels ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) releasing. As expected, EGCG ameliorated Oxyhemoglobin (OxyHb)-induced impaired mitochondrial dynamics by regulation the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the elevated fragmented mitochondria and mtDNA copy number in OxyHb group almost to normal level after SAH. In addition, the normal autophagic flux induced by EGCG both at the initiation and formation stages by regulating Atg5 and Beclin-1 after SAH to timely eliminate damaged mitochondria. In the end, EGCG increased the neurological score by decreased cell death via cyt c mediated intrinsic apoptotic pathway. The results shed light on the mechanisms behind the neuroprotective effects of EGCG by inhibiting the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, simultaneously inhibiting and timely eliminating damaged mitochondria could determine the therapeutic effect of EGCG.

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Publication details

The article was received on 25 Jul 2018, accepted on 04 Oct 2018 and first published on 31 Oct 2018


Article type: Paper
DOI: 10.1039/C8FO01497C
Citation: Food Funct., 2018, Accepted Manuscript
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    Evaluation of the neuroprotective effect of EGCG: a potential mechanism of mitochondrial dysfunction and mitochondrial dynamics after subarachnoid hemorrhage

    Y. Chen, J. Chen, X. Sun, X. Shi, L. Wang, L. Huang and W. Zhou, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C8FO01497C

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