Motaghinejad Majid, Motevalian Manijeh, Fatima Sulail, Hashemi Hajar, Gholami Mina
Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Biomed Pharmacother. 2017 Mar;87:721-740. doi: 10.1016/j.biopha.2016.12.020. Epub 2017 Jan 14.
Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear.
Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting.
Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters.
Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway.
酒精滥用会对脑神经元造成严重损害。研究报告了姜黄素对酒精诱导的神经退行性变具有神经保护作用。然而，其确切作用机制仍不清楚。
将70只大鼠平均分为7组（每组10只）。第1组给予生理盐水（0.7ml/只），第2组给予酒精（2g/kg/天），持续21天。第3、4、5和6组同时给予酒精（2g/kg/天）和姜黄素（分别为10、20、40和60mg/kg），持续21天。第7组动物自行摄入酒精21天。第8组单独用姜黄素（60mg/kg，腹腔注射）治疗21天。采用旷场试验（OFT）研究大鼠的运动活性。评估海马体的氧化、抗氧化和炎症因子。此外，通过逆转录聚合酶链反应（RT-PCR）在基因水平研究脑环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）水平。另外，通过蛋白质印迹法测定BDNF、CREB、磷酸化CREB（CREB-P）、Bax和Bcl-2的蛋白表达。
自愿和非自愿给予酒精会改变旷场试验中的运动活性，姜黄素治疗可抑制这种酒精诱导的运动障碍。此外，给予酒精会增加离体海马组织中的脂质过氧化、线粒体氧化型谷胱甘肽（GSSG）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和Bax水平。此外，观察到酒精会导致还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）活性以及CREB、BDNF和Bcl-2水平显著降低。单独使用姜黄素也不会改变行为以及生化和分子参数。
姜黄素可能通过激活CREB-BDNF信号通路，作为一种神经保护剂对抗酒精滥用的神经退行性影响。
