Evidence map›Paper›PMID 40892063›Full record

ArticleArchives of toxicology2025

The deglycosylated metabolite of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D- glucoside contributes to immune-mediated hepatotoxicity induced by Polygonum multiflorum.

Ying Li, Yuwei Hu, Xiaoli Meng, Paul Thomson, Dongsheng Ouyang, Dean Naisbitt, Tai Rao

Abstract read
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In one paragraph

Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ying LiDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, N0. 110 Xiangya Road, Changsha, 410078, China.
Yuwei HuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, N0. 110 Xiangya Road, Changsha, 410078, China.
Xiaoli MengDepartment of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L693GE, UK.
Paul ThomsonDepartment of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L693GE, UK.
Dongsheng OuyangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, N0. 110 Xiangya Road, Changsha, 410078, China.
Dean NaisbittDepartment of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L693GE, UK. dnes@liverpool.ac.uk.
Tai RaoDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, N0. 110 Xiangya Road, Changsha, 410078, China. raotai9298@csu.edu.cn.ORCID 0000-0003-2515-8886

Funding

China Scholarship Council 202006375022National Natural Science Foundation of China 81803837National Natural Science Foundation of China 82274032
6 · The paper itself

Abstract

Polygonum multiflorum (PM) has been reported to cause immune-mediated idiosyncratic liver injury. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) has been identified as a hepatotoxic constituent responsible for PM-induced hepatotoxicity. Covalent protein modification by reactive metabolites plays a crucial role in herb and drug-induced liver injury. Whether it is essential for the hepatotoxicity of THSG needs further clarification. THSG can be hydrolyzed into its aglycone 2,3,5,4'-tetrahydroxystilbene (THS). This study aims to investigate the impact of THS on liver injury and elucidate its underlying mechanism. Metabolism of THSG and covalent modification of cysteine residues by THS were identified by mass spectrometry and proteomics. Hepatotoxicity and T-cell immune response induced by THS were evaluated in vitro and in vivo. The immunological mechanism was investigated using PBMC from healthy donors. THS was detected in both the liver and blood samples after oral administration of THSG to mice. Cysteine-based covalent modification of glutathione (GSH), glutathione S-transferase Pi (GSTP) and hepatic proteins by THS was identified. Liver injury accompanied by inflammatory cell infiltration and T-cell activation were observed in vivo and in vitro with THS treatment. PBMCs from healthy donors and drug-specific T-cell clones (TCCs) could be activated by THS possibly through the hapten pathway. THS, the deglycosylated metabolite of THSG, functions as a hapten by covalently binding to proteins to induce cellular stress and activate T-cells, which may contribute to PM-induced hepatotoxicity.

Indexed as

Chemical and Drug Induced Liver InjuryFallopia multifloraGlucosidesStilbenesAnimalsHumansLiverMaleMiceMice, Inbred C57BLT-Lymphocytes2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranosideGlucosidesStilbenes2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucosideCovalent protein bindingHepatotoxicityPolygonum multiflorumT-cell immune response

Identifiers

PMID40892063

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.