|
| Preliminary exploration of HepaRG cytotoxicity mechanism of Isobavachalcone based on non targeted metabolomics |
| Hits 119 Download times 36 Received:November 20, 2025 |
| View Full Text View/Add Comment Download reader |
| DOI
10.11656/j.issn.1673-9043.2026.02.06 |
| Key Words
isobavachalcone;untargeted metabolomics;hepatotoxicity;stoichiometry;enrichment analysis |
| Author Name | Affiliation | E-mail | | MA Shuyue | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WANG Aixi | 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 | | | SHEN Rong | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | DONG Yutong | 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 | | | ZHOU Kun | Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | z.k.ken@263.net |
|
| Abstract
|
| [Objective] To investigate the mechanism of hepatotoxicity of human hepatoma-derived progenitor cells （HepaRG）induced by isobavachalcone（IBC）based on metabolomics technology. [Methods] The effect of IBC on HepaRG cell viability was detected by MTT assay，and the half maximal inhibitory concentration（IC50）value was calculated. The metabolites of HepaRG cell supernatants after 24 h of IBC intervention were detected using the Triple TOFTM 5600 system，and multivariate statistical methods，such as principal component analysis，orthogonal partial least squares discriminant analysis，and cluster analysis，were used to screen for differential metabolites between each dosing group and the control group. Metabolic pathway enrichment analysis was then performed on these differential metabolites. [Results] With the increase of IBC dosage，the cell viability of HepaRG significantly decreased. At 30 μmol/L，significant cytotoxicity was observed（P<0.001）；compared with the control group，when the drug concentration reached 24.53 μmol/L，the cell viability decreased by 10%；at 41.22 μmol/L，cell viability decreased by 90%. By calculation，its IC50 was determined to be 32.89 μmol / L，indicating that IBC has strong hepatotoxic effects. Enrichment analysis showed that IBC-induced HepaRG cell damage was mainly enriched in pathways such as phenylalanine，tyrosine，and tryptophan biosynthesis，valine，leucine，and isoleucine biosynthesis， and histidine metabolism（P<0.001）. [Conclusion] Isobavachalcone can significantly inhibit the activity of HepaRG cells and induce liver cell injury by affecting cellular metabolites such as phenylalanine，histidine，arginine，and lysine，as well as the biosynthetic metabolic pathways of phenylalanine，arginine，valine，leucine，and isoleucine. |
|
|
|
|
|
