In-silico discovery of the hapten-based interaction between idiosyncratic hepatotoxic ingredients of Polygonum multiflorum and HLA-B*35:01 DOI Creative Commons
Dake Xiao, Xu Zhao, Xiaoyan Zhan

и другие.

Science of Traditional Chinese Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract Background The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8- O-β -D-glucoside (EG) 2,3,5,4′-tetrahydroxystilbene-2- have been proposed potential contributory ingredients in pathogenesis PM-IDILI. However, precise mechanisms through which these susceptible factors contribute to development remain unclear. Objectives This study aims explore molecular characteristics PM-DILI propose mechanistic hypothesis based on our PM-induced protein adducts. Methods Key differences between general Chinese HLA-B alleles were comparing sequences, peptide binding motifs, structures. Molecular docking was employed assess whether haptenated peptides can be presented other related alleles. simplified dipeptide model used evaluate affinity EG-haptenated peptides. Results Our findings revealed significant residues B F pockets compared Further analysis suggested pocket capable EG-cysteine adducts might key feature pathogenesis. Peptide using DINC dynamics simulations indicated could form stable complexes also highlighted critical roles both binding. Specifically, binds EG-modified residue peptides, while pocket, despite lacking shared features among patients, may indirectly influence incidence filtering cysteine experimentally validated dipeptide-based assay, confirming bind Conclusions unique These suggest hapten-based drug hypersensitivity reaction driven EG, providing theoretical framework for further aimed at elucidating underlying

Язык: Английский

In-silico discovery of the hapten-based interaction between idiosyncratic hepatotoxic ingredients of Polygonum multiflorum and HLA-B*35:01 DOI Creative Commons
Dake Xiao, Xu Zhao, Xiaoyan Zhan

и другие.

Science of Traditional Chinese Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract Background The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8- O-β -D-glucoside (EG) 2,3,5,4′-tetrahydroxystilbene-2- have been proposed potential contributory ingredients in pathogenesis PM-IDILI. However, precise mechanisms through which these susceptible factors contribute to development remain unclear. Objectives This study aims explore molecular characteristics PM-DILI propose mechanistic hypothesis based on our PM-induced protein adducts. Methods Key differences between general Chinese HLA-B alleles were comparing sequences, peptide binding motifs, structures. Molecular docking was employed assess whether haptenated peptides can be presented other related alleles. simplified dipeptide model used evaluate affinity EG-haptenated peptides. Results Our findings revealed significant residues B F pockets compared Further analysis suggested pocket capable EG-cysteine adducts might key feature pathogenesis. Peptide using DINC dynamics simulations indicated could form stable complexes also highlighted critical roles both binding. Specifically, binds EG-modified residue peptides, while pocket, despite lacking shared features among patients, may indirectly influence incidence filtering cysteine experimentally validated dipeptide-based assay, confirming bind Conclusions unique These suggest hapten-based drug hypersensitivity reaction driven EG, providing theoretical framework for further aimed at elucidating underlying

Язык: Английский

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