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| Study on the hepatotoxicity of neobavaisoflavone based on 3D culture of heparg cells and metabolomics |
| Hits 76 Download times 47 Received:December 20, 2025 |
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| DOI
10.11656/j.issn.1673-9043.2026.06.07 |
| Key Words
neobavaisoflavone;hepatotoxicity;HepaRG cells;3D-culture;metabolomics;lipid metabolism |
| Author Name | Affiliation | E-mail | | PEI Tianxian | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | XI Hengyu | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | ZHANG Zhou | Tianjin Tiancheng New Drug Evaluation Co., Ltd., Tianjin 300301, China | | | WANG Yihan | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | MA Chao | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WANG Xuetong | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | ZHOU Kun | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
National Key Laboratory of Chinese Medicine Modernization, Tianjin 301617, China
State Key Laboratory of Component-based Chinese Medicine, Tianjin 301617, China | z.k.ken@263.net |
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| Abstract
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| [Objective] To investigate the hepatotoxicity of neobavaisoflavone（NBIF） and explore its potential mechanism based on 3D culture of HepaRG cells and metabolomics technology. [Methods] HepaRG cells were subjected to 3D culture for 4 days，followed by treatment with NBIF at concentrations of 0，2.5，5，and 10 μmol/L once daily for 5 consecutive days. At 24 h after the first and fifth administrations，the viability of HepaRG cells was determined by the CCK-8 assay. At 24 h after the fifth administration，the apoptosis rate of HepaRG cells was detected by flow cytometry. Ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS） combined with multivariate statistical analysis was employed to analyze the metabolic profiles of cell supernatants，so as to screen differential metabolites and related metabolic pathways. [Results] With the increase of NBIF concentration and administration frequency，the viability of 3D-cultured HepaRG cells decreased significantly. Compared with the control group（6.86%），the early apoptosis rates of HepaRG cells in the 5 μmol/L（11.56%） and 10 μmol/L（28.44%） NBIF groups were notably elevated. A total of 17 differential metabolites with downregulated levels were identified in the NBIF-treated groups compared with the control group. Moreover，5，6，and 6 metabolic pathways were involved in the 2.5，5 and 10 μmol/L NBIF groups，respectively. [Conclusion] NBIF can reduce the viability and increase the apoptosis rate of 3D-cultured HepaRG cells. Its hepatotoxic mechanism may be associated with the disorder of multiple metabolic pathways，including the biosynthesis of phenylalanine，tyrosine and tryptophan，phenylalanine metabolism，as well as the biosynthesis of fatty acids and unsaturated fatty acids. |
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