JOURNALS
2026
2.
Kwanyong Choi; Jun Young Park; Sunyong Yoo; Soo-yeon Park; Hyoung-Yun Han; Ji Yeon Kim
Abstract | Links | BibTeX | Dimensions | Tags: Drug-induced liver injury, in silico, in vitro
@article{nokey,
title = {Combining UHPLC profiling and random walk network-based in vitro analysis to predict herb-induced liver injury},
author = {Kwanyong Choi; Jun Young Park; Sunyong Yoo; Soo-yeon Park; Hyoung-Yun Han; Ji Yeon Kim},
url = {https://doi.org/10.1016/j.fct.2026.116050},
doi = {10.1016/j.fct.2026.116050},
issn = {1873-6351},
year = {2026},
date = {2026-06-01},
urldate = {2026-06-01},
journal = {Food and Chemical Toxicology},
volume = {212},
number = {116050},
abstract = {Herbal medicines are widely used, yet their hepatotoxic potential remains underexplored in predictive toxicology. UHPLC-based compound profiling was combined with a Random Walk with Restart (RWR) network approach using herb compound target associations filtered by P-value and Z-score thresholds. Predictions were evaluated in HepG2 cells using microscopy-based phenotypic assessment, mitochondrial membrane potential measurement, ALT and AST activities in culture supernatants, transcriptomic profiling by RNA sequencing with enrichment analysis, and qRT-PCR as supportive validation. RWR prioritized apoptosis, oxidative stress, and inflammatory pathways for Camellia sinensis, Piper longum, Atractylodes lancea, Angelica gigas, Xanthium sibiricum, and Cynanchum wilfordii, whereas Astragalus membranaceus showed limited enrichment. Consistent with these predictions, the six prioritized extracts induced injury-associated morphological changes, loss of mitochondrial membrane potential, and increased ALT and AST release, while A. membranaceus showed minimal changes. RNA sequencing showed broad transcriptomic perturbations and clustering of the predicted hepatotoxic extracts with coordinated changes across hepatotoxicity-relevant gene categories. Overall, this framework supports scalable preclinical screening of herbal products by linking computational pathway prioritization with experimental validation, and broader herb–compound–target coverage with expanded toxicological datasets may further improve predictive performance for safety assessment.},
note = {Correspondence to Ji Yeon Kim},
keywords = {Drug-induced liver injury, in silico, in vitro},
pubstate = {published},
tppubtype = {article}
}
Herbal medicines are widely used, yet their hepatotoxic potential remains underexplored in predictive toxicology. UHPLC-based compound profiling was combined with a Random Walk with Restart (RWR) network approach using herb compound target associations filtered by P-value and Z-score thresholds. Predictions were evaluated in HepG2 cells using microscopy-based phenotypic assessment, mitochondrial membrane potential measurement, ALT and AST activities in culture supernatants, transcriptomic profiling by RNA sequencing with enrichment analysis, and qRT-PCR as supportive validation. RWR prioritized apoptosis, oxidative stress, and inflammatory pathways for Camellia sinensis, Piper longum, Atractylodes lancea, Angelica gigas, Xanthium sibiricum, and Cynanchum wilfordii, whereas Astragalus membranaceus showed limited enrichment. Consistent with these predictions, the six prioritized extracts induced injury-associated morphological changes, loss of mitochondrial membrane potential, and increased ALT and AST release, while A. membranaceus showed minimal changes. RNA sequencing showed broad transcriptomic perturbations and clustering of the predicted hepatotoxic extracts with coordinated changes across hepatotoxicity-relevant gene categories. Overall, this framework supports scalable preclinical screening of herbal products by linking computational pathway prioritization with experimental validation, and broader herb–compound–target coverage with expanded toxicological datasets may further improve predictive performance for safety assessment.
2024
1.
Kwanyong Choi; Soyeon Lee; Sunyong Yoo; Hyoung-Yun Han; Soo-yeon Park; Ji Yeon Kim
Abstract | Links | BibTeX | Dimensions | Tags: Drug-induced liver injury, in silico, in vitro
@article{nokeye,
title = {Prediction of bioactive compounds hepatotoxicity using in silico and in vitro analysis},
author = {Kwanyong Choi and Soyeon Lee and Sunyong Yoo and Hyoung-Yun Han and Soo-yeon Park and Ji Yeon Kim},
doi = {10.1186/s13765-024-00961-z},
year = {2024},
date = {2024-12-17},
urldate = {2024-12-17},
journal = {Applied Biological Chemistry},
volume = {67},
number = {107},
abstract = {The leading safety issue and side effect associated with natural herb products is drug-induced liver injury (DILI) caused by bioactive compounds derived from the herb products. Herein, in silico and in vitro analyses were compared to determine the hepatotoxicity of compounds. The results of in silico analyses, which included an integrated database and an interpretable DILI prediction model, identified calycosin, biochanin_A, xanthatin, piperine, and atractyloside as potential hepatotoxic compounds and tenuifolin as a non-hepatotoxic compound. To evaluate the viability of HepG2 cells exposed to the selected compounds, we determined the IC50 and IC20 values of viability using MTT assays. For in-depth screening, we performed hematoxylin and eosin-stained morphological screens, JC-1 mitochondrial assays, and mRNA microarrays. The results indicated that calycosin, biochanin_A, xanthatin, piperine, and atractyloside were potential hepatotoxicants that caused decreased viability and an apoptotic phase in morphology, while these effects were not observed for tenuifolin, a non-hepatotoxicant. In the JC-1 assay, apoptosis was induced by all the predicted hepatotoxicants except atractyloside. According to transcriptomic analysis, all the compounds predicted to induce DILI showed hepatotoxic effects. These results highlighted the importance of using in vitro assays to validate predictive in silico models and determine the potential of bioactive compounds to induce hepatotoxicity in humans.},
note = {Correspondence to Ji Yeon Kim},
keywords = {Drug-induced liver injury, in silico, in vitro},
pubstate = {published},
tppubtype = {article}
}
The leading safety issue and side effect associated with natural herb products is drug-induced liver injury (DILI) caused by bioactive compounds derived from the herb products. Herein, in silico and in vitro analyses were compared to determine the hepatotoxicity of compounds. The results of in silico analyses, which included an integrated database and an interpretable DILI prediction model, identified calycosin, biochanin_A, xanthatin, piperine, and atractyloside as potential hepatotoxic compounds and tenuifolin as a non-hepatotoxic compound. To evaluate the viability of HepG2 cells exposed to the selected compounds, we determined the IC50 and IC20 values of viability using MTT assays. For in-depth screening, we performed hematoxylin and eosin-stained morphological screens, JC-1 mitochondrial assays, and mRNA microarrays. The results indicated that calycosin, biochanin_A, xanthatin, piperine, and atractyloside were potential hepatotoxicants that caused decreased viability and an apoptotic phase in morphology, while these effects were not observed for tenuifolin, a non-hepatotoxicant. In the JC-1 assay, apoptosis was induced by all the predicted hepatotoxicants except atractyloside. According to transcriptomic analysis, all the compounds predicted to induce DILI showed hepatotoxic effects. These results highlighted the importance of using in vitro assays to validate predictive in silico models and determine the potential of bioactive compounds to induce hepatotoxicity in humans.