Journal
LIFE SCIENCES
Volume 157, Issue -, Pages 97-106Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.05.032
Keywords
Phellodendrine; AAPH; Zebrafish embryo; Oxidative stress; AKT/NF-kappa B
Funding
- Specialized Research Fund for the Doctoral Program of Higher Education [20130182110023]
- High-end Engineering and Technical Personnel Training Plan of Chongqing
- Major Program of Chongqing Educational Commission [KJZH14203]
- County-University Cooperation Innovation funds of Southwest University [Sz201501, Sz201401]
- special program for Scientific and Technical Innovation of Chongqing Social Livelihood [cstc2015shmszx80012]
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Aims: This study is to investigate the effect of phellodendrine (PHE) against AAPH-induced oxidative stress and find out the biological mechanism of PHE by using the zebrafish embryo model. Main methods: After treatments by AAPH or PHE, the mortality and heartbeat of zebrafish embryos were recorded and the production of reactive oxygen species (ROS), lipid-peroxidation and the rate of cell death were detected by fluorescence spectrophotometry respectively. Whereafter, the pathways of PHE against AAPH-induced oxidative stress were screened by inhibitors to explore its biological mechanism. The related genes and proteins expressions were analyzed by real-time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and western blotting. Key findings: The PHE obviously improved the decreased survival rate and abnormally elevated heart-beating rate of zebrafish embryos caused by AAPH. Especially 200 mu g/mL of PHE make the survival rate increased to 90.26 +/- 1.40% at 72 hfp and the heartbeat back to normal. Besides, AAPH caused a significant increase in the production of reactive oxygen species (ROS), lipid-peroxidation and cell death rate, all of which could be decreased after PHE treatment dose-dependently. And PHE exerted the protective activity against AAPH-induced oxidative stress through down-regulating AKT phosphorylation and NF-kB(3) expression, which associate with modulation of IKK phosphorylation in zebrafish embryos. Significance: The PHE showed a good antioxidant effect in vivo, and the mechanism has been stated that the PHE can down-regulating AKT, IKK, NF-kB phosphorylation and COX-2 expression induced by AAPH. Moreover, the PHE also ameliorated the ROS-mediated inflammatory response. (C) 2016 Elsevier Inc. All rights reserved.
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