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Protective effects of 6,7,4′-trihydroxyisoflavone, a major metabolite of daidzein, on 6-hydroxydopamine-induced neuronal cell death in SH-SY5Y human neuroblastoma cells

  • Yong-Hyun Ko
  • Seung-Hwan Kwon
  • Seon-Kyung Kim
  • Bo-Ram Lee
  • Kwang-Hyun Hur
  • Young-Jung Kim
  • Seong-Eon Kim
  • Seok-Yong Lee
  • Choon-Gon JangEmail author
Research Article

Abstract

Daidzein, one of the important isoflavones, is extensively metabolized in the human body following consumption. In particular, 6,7,4′-trihydroxyisoflavone (THIF), a major metabolite of daidzein, has been the focus of recent investigations due to its various health benefits, such as anti-cancer and anti-obesity effects. However, the protective effects of 6,7,4′-THIF have not yet been studied in models of Parkinson’s disease (PD). Therefore, the present study aimed to investigate the protective activity of 6,7,4′-THIF on 6-hydroxydopamine (OHDA)-induced neurotoxicity in SH-SY5Y human neuroblastoma cells. Pretreatment of SH-SY5Y cells with 6,7,4′-THIF significantly inhibited 6-OHDA-induced neuronal cell death, lactate dehydrogenase release, and reactive oxygen species production. In addition, 6,7,4′-THIF significantly attenuated reductions in 6-OHDA-induced superoxide dismutase activity and glutathione content. Moreover, 6,7,4′-THIF attenuated alterations in Bax and Bcl-2 expression and caspase-3 activity in 6-OHDA-induced SH-SY5Y cells. Furthermore, 6,7,4′-THIF significantly reduced 6-OHDA-induced phosphorylation of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase 1/2. Additionally, 6,7,4′-THIF effectively prevented 6-OHDA-induced loss of tyrosine hydroxylase. Taken together, these results suggest that 6,7,4′-THIF, a major metabolite of daidzein, may be an attractive option for treating and/or preventing neurodegenerative disorders such as PD.

Keywords

6,7,4′-Trihydroxyisoflavone 6-Hydroxydopamine Oxidative stress Apoptosis Parkinson’s disease 

Notes

Acknowledgements

This work was supported by a Grant (NRF-2012R1A5A2A28671860) from the Basic Science Research Program through the National Research Foundation of Korea.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  • Yong-Hyun Ko
    • 1
  • Seung-Hwan Kwon
    • 1
  • Seon-Kyung Kim
    • 1
  • Bo-Ram Lee
    • 1
  • Kwang-Hyun Hur
    • 1
  • Young-Jung Kim
    • 1
  • Seong-Eon Kim
    • 1
  • Seok-Yong Lee
    • 1
  • Choon-Gon Jang
    • 1
    Email author
  1. 1.Department of Pharmacology, School of PharmacySungkyunkwan UniversitySuwonRepublic of Korea

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