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姜黄素通过激活自噬和改善涉及Nrf2/HO-1信号通路的炎症,对黄曲霉毒素诱导的毒性发挥肝脏保护作用。

Curcumin confers hepatoprotection against AFB-induced toxicity via activating autophagy and ameliorating inflammation involving Nrf2/HO-1 signaling pathway.

作者信息

Muhammad Ishfaq, Wang Xinghe, Li Sihong, Li Rui, Zhang Xiuying

机构信息

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, 150030, Heilongjiang, People's Republic of China.

Laboratory of Veterinary Pathology, Faculty of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, People's Republic of China.

出版信息

Mol Biol Rep. 2018 Dec;45(6):1775-1785. doi: 10.1007/s11033-018-4323-4. Epub 2018 Aug 24.

Abstract

The current study demonstrated curcumin intervention against AFB-indeuced hepatotoxicity. The hallmarks of autophagy and inflammation were assessed by transmission electron microscopy, RT-PCR and western blot. Besides, normal cellular morphology, autophagosomes were found in control and curcumin control group. In contrast, fragmented and swollen mitochondria, irregular shaped nuclei and fat droplets were visible but autophagosomes disappear in AFB-treated group. The mRNA and protein expression levels of autophagy-related genes indicated that AFB significantly inhibited autophagy and induced inflammation. In addition, Nrf2 and HO-1 mRNA and protein level was significantly (p < 0.05) reduced in AFB-fed group. Intriguingly, dietary curcumin supplementation modulated autophagy through the activation of beclin-1, ATG5, Dynein, LC3a, LC3b-I/II and downregulation of p53 & mTOR expression level. Curcumin significantly ameliorated AFB-induced inflammation. Moreover, curcumin treatment significantly (p < 0.05) elevated AFB-induced decrease in Nrf2 and HO-1 mRNA and protein expression level. In summary, curcumin activated autophagy and ameliorated inflammation involving Nrf2 signaling pathway which may become a new targeted therapy to prevent AFB-induced hepatotoxicity.

摘要

当前研究证明了姜黄素对黄曲霉毒素诱导的肝毒性具有干预作用。通过透射电子显微镜、逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法评估自噬和炎症的特征。此外,在对照组和姜黄素对照组中发现了正常的细胞形态和自噬体。相比之下,在黄曲霉毒素处理组中可见线粒体碎片化和肿胀、细胞核形状不规则以及脂肪滴,但自噬体消失。自噬相关基因的mRNA和蛋白质表达水平表明,黄曲霉毒素显著抑制自噬并诱导炎症。此外,在喂食黄曲霉毒素的组中,Nrf2和HO-1的mRNA和蛋白质水平显著降低(p < 0.05)。有趣的是,饮食中补充姜黄素通过激活贝克林1(beclin-1)、自噬相关蛋白5(ATG5)、动力蛋白(Dynein)、微管相关蛋白1轻链3α(LC3a)、微管相关蛋白1轻链3β-I/II(LC3b-I/II)以及下调p53和雷帕霉素靶蛋白(mTOR)的表达水平来调节自噬。姜黄素显著改善了黄曲霉毒素诱导的炎症。此外,姜黄素处理显著(p < 0.05)提高了黄曲霉毒素诱导的Nrf2和HO-1 mRNA及蛋白质表达水平的降低。总之,姜黄素激活自噬并改善涉及Nrf2信号通路的炎症,这可能成为预防黄曲霉毒素诱导的肝毒性的一种新的靶向治疗方法。

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