Xiao Jia, Wang Jiteng, Xing Feiyue, Han Tao, Jiao Rui, Liong Emily C, Fung Man-Lung, So Kwok-Fai, Tipoe George L
Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China; Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
School of Fishery, Zhejiang Ocean University, Zhoushan, China.
PLoS One. 2014 Apr 16;9(4):e95214. doi: 10.1371/journal.pone.0095214. eCollection 2014.
In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-κB) through the restoration of its inhibitor kappa B alpha (IκBα), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases.
在本研究中,评估了二棕榈酸玉米黄质(ZD)对大鼠酒精性脂肪肝病(AFLD)模型的治疗效果。在大鼠为期10周的乙醇灌胃给药过程中,从第5周开始至第10周用ZD进行治疗,显著减轻了典型的AFLD症状,包括大鼠体重减轻、肝脏脂肪滴积累、氧化应激、炎症、趋化反应以及肝脏细胞凋亡的发生。ZD减轻肝功能异常部分是通过降低细胞色素P450 2E1(CYP2E1)的表达水平,通过恢复其抑制剂κBα(IκBα)来降低核因子κB(NF-κB)的活性,以及调节包括p38丝裂原活化蛋白激酶(p38 MAPK)、应激活化蛋白激酶(JNK)和细胞外信号调节激酶(ERK)在内的丝裂原活化蛋白激酶(MAPK)信号通路。单独使用ZD对健康大鼠没有明显的不良影响。在细胞AFLD模型中,我们还证实抑制p38 MAPK和ERK消除了ZD的有益作用。这些结果为使用玉米黄质及其衍生物作为预防和治疗酒精性肝病的新型辅助药物提供了科学依据。