, Volume 18, Issue 7, pp 811–824 | Cite as

Delphinidin prevents hypoxia-induced mouse embryonic stem cell apoptosis through reduction of intracellular reactive oxygen species-mediated activation of JNK and NF-κB, and Akt inhibition

  • Bit Na Seo
  • Jung Min Ryu
  • Seung Pil Yun
  • Ji Hoon Jeon
  • Su Shin Park
  • Keon Bong Oh
  • Jin-Ki Park
  • Ho Jae HanEmail author
Original Paper


Delphinidin, gallic acid, betulinic acid, and ursolic acid, which are bio-active ingredients in a variety of fruits, vegetables, and herbs, have potent antioxidant activity and various biological activities. However, it is not clear whether these bio-active ingredients can significantly contribute to the protection of embryonic stem (ES) cells from hypoxia-induced apoptosis. In the present study, hypoxia-induced ES cells apoptosis with time, which were abrogated by pretreatment with all ingredients. Hypoxia-induced ROS generation was blocked by pretreatment with all ingredients in a dose-dependent manner, with the maximum ROS scavenging effect observed for delphinidin. Hypoxia increased phosphorylation of JNK and NF-κB were blocked by pretreatment of delphinidin as well as NAC. Hypoxia decreased phosphorylation of Aktthr308 and ser473; these decreases were reversed by pretreatment with delphinidin or NAC. However, Akt inhibition did not affect NF-κB phosphorylation. Delphinidin attenuated the hypoxia-induced increase in Bax, cleaved caspase-9, cleaved caspase-3, and decrease in Bcl-2, which were diminished by pretreatment of Akt inhibitor. Hypoxia induced Bax translocation from the cytosol to mitochondria. Furthermore, hypoxia induced mitochondria membrane potential loss and cytochrome c release in cytosol, which were blocked by delphinidin pretreatment. Hypoxia induced cleavage of procaspase-9 and procaspase-3 which were blocked by delphinidin or SP600125, but Akt inhibitor abolished the protection effect of delphinidin. Moreover, inhibition of JNK and NF-κB abolished hypoxia-induced ES cell apoptosis and inhibition of Akt attenuated delphinidin-induced blockage of apoptosis. The results indicate that delphinidin can prevent hypoxia-induced apoptosis of ES cells through the inhibition of JNK and NF-κB phosphorylation, and restoration of Akt phosphorylation.


Delphinidin Apoptosis Hypoxia Embryonic stem cells 



This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009090), Rural Development Administration, the Health Technology R&D project (A120216), Ministry of Health and Welfare, and Research Settlement Fund (550-20110054) for the new faculty of SNU, Republic of Korea.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Bit Na Seo
    • 1
  • Jung Min Ryu
    • 1
  • Seung Pil Yun
    • 1
  • Ji Hoon Jeon
    • 1
  • Su Shin Park
    • 1
  • Keon Bong Oh
    • 2
  • Jin-Ki Park
    • 2
  • Ho Jae Han
    • 1
    Email author
  1. 1.Department of Veterinary PhysiologyCollege of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National UniversitySeoulSouth Korea
  2. 2.Animal Biotechnology DivisionNational Institute of Animal Science, RDASuwonSouth Korea

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