Chinese Journal of Pharmacovigilance ›› 2019, Vol. 16 ›› Issue (7): 385-392.

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Hepatotoxicity Evaluation of Polygonum Multiflorum Based on 2D and 3D Hepatocyte Models In Vitro

YAN Yujing1, DAN Mo1, WANG Qi2,*, WEN Hairuo1,*   

  1. 1 National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing 100176, China;
    2 Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2019-08-06 Revised:2019-08-06 Online:2019-07-20 Published:2019-08-06

Abstract: Objective To evaluate the hepatotoxicity of PMEE and THSG on 2D and 3D hepatocyte models in vitro and compare the differences between them. Methods 2D and 3D hepatocyte models were dealt with different concentrations of PMEE and THSG for 24 h, 48 h and 144 h, then the cell viability, DNA damage and cell apoptosis were detected. Results PMEE could inhibit the proliferation of HepaRG in 2D model notably, but the effect on 3D model was not like this. Compared with 3D model, PMEE also had a stronger DNA damage effect on 2D model. The inhibitory effect of THSG on HepaRG in 3D model was greater than that in 2D model. What' s more, the frequency of apoptosis cells of high-dose THSG group was increased notably compared with control group in the alkaline comet assay of 3D model (P <0.01). Conclusion 3D model was greater than 2D model in sensitivity. Both PMEE and THSG had hepatotoxicity and the hepatotoxicity of PMEE was attenuated after being metabolized by 3D hepatocyte models, THSG was the opposite.

Key words: polygonum multiflorum, stilbene glycoside, hepatotoxicity, two-dimension culture, three-dimension culture

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