Tetrahydrocurcumin reduces oxidative stress-induced apoptosis via the mitochondrial apoptotic pathway by modulating autophagy in rats after traumatic brain injury.

作者：Yongyue Gao, Zong Zhuang, Shanting Gao, Xiang Li, Zihuan Zhang, Zhen-Nan Ye, Liwen Li, Chao Tang, Meng‐Liang Zhou, Xiao Han, Jie Li · 发表于：PubMed · 年份：2017 · 被引用次数：71 · 研究领域：Autophagy in Disease and Therapy、Heme Oxygenase-1 and Carbon Monoxide、Curcumin's Biomedical Applications

Tetrahydrocurcumin (THC) has been identified as a multi-functional neuroprotective agent in numerous neurological disorders. Oxidative stress as a result of injury may induce neuronal apoptosis after traumatic brain injury (TBI). Treatment with THC may improve neurological function following TBI by attenuating oxidative stress and apoptosis and by enhancing autophagy. The purpose of this study was to investigate the mechanism of neuroprotection by THC against oxidative stress-induced neuronal apoptosis after TBI. We hypothesized that neuroprotection by THC may involve modulation of autophagy and the mitochondria apoptotic pathway. We used western blot analysis to evaluate the effect of THC on proteins involved in mitochondrial autophagy and apoptosis after TBI. The terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunofluorescence staining were used to confirm the role of THC in apoptosis and autophagy, respectively. THC-induced neuroprotection was assessed by neurological severity scoring (NSS) and by measuring the brain water content. We demonstrated that treatment with THC increased expression of autophagy-associated proteins LC3-II and Beclin-1 at 24 h post-TBI. Treatment with THC also reduced expression of malondialdehyde (MDA) and increased glutathione peroxidase (GPx) activity. Further, treatment with THC attenuated apoptosis by modulating mitochondrial apoptosis and reducing oxidative stress. Treatment with 3-methyladenine (3-MA) mitigat...