title: The defensive effect of phellodendrine against AAPH-induced oxidative stress through regulating the AKT/NF-κB pathway in zebrafish embryos.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  The PHE obviously improved the decreased survival rate and abnormally elevated heart-beating rate of zebrafish embryos caused by AAPH. Especially 200μg/mL of PHE make the survival rate increased to 90.26±1.40% at 72hfp 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-kB3 expression, which associate with modulation of IKK phosphorylation in zebrafish embryos.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tian
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Kou
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ye
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Li
mesh_terms: D000578:Amidines / Q000633:toxicity*; D000818:Animals; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D000578:Amidines; D016328:NF-kappa B; D011807:Quinolizines; C079418:phellodendrine; C046728:2,2'-azobis(2-amidinopropane); D051057:Proto-Oncogene Proteins c-akt
keywords: AAPH; AKT/NF-κB; Oxidative stress; Phellodendrine; Zebrafish embryo