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Protective effect of dihydromyricetin on hyperthermia-induced apoptosis in human myelomonocytic lymphoma cells

  • Qian-Wen Feng
  • Zheng-Guo Cui
  • Yu-Jie Jin
  • Lu Sun
  • Meng-Ling Li
  • Shahbaz Ahmad Zakki
  • De-Jun Zhou
  • Hidekuni InaderaEmail author


Dihydromyricetin (DMY) is a traditional herbal medicine, with a wide range of biological activities. Extreme hyperthermia (HT) can suppress the immune system; thus, protection of the immune system is beneficial in heat-related diseases, including heatstroke. In our study, we revealed the protective effect of DMY against HT-induced apoptosis and analysed the underlying molecular mechanisms. We incubated human myelomonocytic lymphoma U937 cells at 44 °C for 30 min with or without DMY and followed by further incubation for 6 h at 37 °C. Cell viability was determined by the CCK-8 assay. DMY did not cause any cytotoxic effects in U937 cells even at high doses. HT treatment alone induced significant apoptosis, which was detected by DNA fragmentation and Annexin V/PI double staining. Mitochondrial dysfunction was identified by loss of mitochondrial membrane potential (MMP) during heat stimulation. Apoptotic related proteins were involved, truncated Bid and caspase-3 were upregulated, and Mcl-1 and XIAP were downregulated. We also identified the related signalling pathways, such as the MAPK and PI3K/AKT pathways. However, changes in HT were dramatically reversed when the cells were pretreated with DMY before exposure to HT. Overall, MAPKs and PI3K/AKT signalling, mitochondrial dysfunction, and caspase-mediated pathways were involved in the protective effect of DMY against HT-induced apoptosis in U937 cells, which was totally reversed by DMY pretreatment. These findings indicate a new clinical therapeutic strategy for the protection of immune cells during heatstroke.


Dihydromyricetin Hyperthermia Apoptosis Heatstroke Mitochondria 



This work was supported by JSPS KAKENHI Grant No. 18K10044.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interests regarding the publication of this article.

Supplementary material

10495_2019_1518_MOESM1_ESM.pdf (241 kb)
Supplementary material 1 (PDF 240 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Qian-Wen Feng
    • 1
  • Zheng-Guo Cui
    • 1
    • 2
  • Yu-Jie Jin
    • 1
  • Lu Sun
    • 1
  • Meng-Ling Li
    • 1
  • Shahbaz Ahmad Zakki
    • 1
  • De-Jun Zhou
    • 2
  • Hidekuni Inadera
    • 1
    Email author
  1. 1.Department of Public Health, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  2. 2.Graduate School of MedicineHenan Polytechnic UniversityJiaozuoChina

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