The Binding Ability of Aloe-Emodin to Free l-Cysteine on Hepatic Protein-Induced Hepatocyte Toxicity.

Authors

Lingwen Dong, Yanan Liu, Lingge Shi, Boyan Liu, Shiqi Qiu, Xinhang Zhang, Wuxiyar Otkur, Guoxiang Sun, Xu Wang

Published in

Phytochemical analysis : PCA. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Aloe-emodin (AE), as an anthraquinone active component in traditional Chinese medicine, exhibits multiple pharmacological activities, yet its mechanism of hepatotoxicity remains unclear. The purpose of this study was to systematically investigate the molecular mechanism of AE-induced hepatotoxicity, with a specific focus on hepatic protein adduction.
AE was incubated with murine hepatic protein solution, followed by enzymatic digestion and liquid chromatography-tandem mass spectrometry analysis to detect l-cysteine covalent adducts. For in vivo study, mice were administered AE, and the formation of hepatic protein adduction was monitored over time and across different doses. Additionally, buthionine sulfoximine was used as a pretreatment to assess the role of glutathione in the adduction process. Cell experiments were also performed to evaluate the relationship between protein adduct formation and cytotoxicity.
AE-cysteine covalent adducts A1 and A2 were identified both in vitro and in livers of AE-treated mice. In vivo study confirmed dose-dependent formation of AE-cysteine adducts (A1/A2) in mouse liver, peaking at 30 min. Depleting glutathione elevated A1 and A2 levels by 40.43% and 27.93% in vivo, indicating the protective role of glutathione through competitively conjugating with AE, thereby reducing its covalent modification of hepatic proteins. Cytotoxicity of AE is positively correlated with its concentration, which reveals the critical role of adduct formation in initiating dosage-dependent cytotoxicity.
This study demonstrates that hepatotoxicity of AE is directly associated with the formation of covalent adducts targeting l-cysteine residues, providing a critical theoretical foundation for safety evaluation and clinical application of AE-containing herbs.

PMID:
42444304
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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