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Abstract

Introduction

The key toxicological constituents and mechanisms of and its formulations, such as Xianling Gubao Capsules (XLGB) and Zhuanggu Guanjie Pills (ZGGJ), remain insufficiently understood, particularly when used in combination. The objective of this study is to investigate the hepatotoxic effects and mechanisms of and its formulations, XLGB and ZGGJ, using network toxicology, molecular docking, and validation.

Materials and Methods

Potential hepatotoxic components and targets of , XLGB, and ZGGJ were screened from multiple databases. PPI networks were constructed, and GO/KEGG enrichment analyses were performed. Molecular docking was used to assess the binding affinities between key components and core targets. validation was conducted using HepG2 cells to assess cell viability and ROS levels through CCK-8 and HCS assays, respectively.

Results

This study confirms that Sagittatoside A, Epimedin B, and Icariside I are the primary hepatotoxic constituents of , capable of targeting core pathways involving KDR, AR, PTGS2, F7, and DPP4. Furthermore, Sagittatoside A and Icariside I significantly elevated ROS levels. The toxic constituents of XLGB and ZGGJ overlapped with those of , and Bavachinin and Neobavaisoflavone from PCL were found to exert synergistic hepatotoxic effects. Neobavaisoflavone enhanced the hepatotoxicity of Epimedin B and Icariside I, while Bavachinin showed synergistic toxicity when combined with Sagittatoside A.

Discussion

Molecular docking confirmed strong binding affinities between these compounds and their targets. In vitro experiments demonstrated that Sagittatoside A and Icariside I significantly increased ROS levels. The compound formulations XLGB and ZGGJ shared similar hepatotoxic components and mechanisms. Additionally, Bavachinin and Neobavaisoflavone from PCL synergistically enhanced the hepatotoxicity of monomers, providing a modern scientific basis for evaluating compatibility principles in traditional Chinese medicine.

Conclusion

This study comprehensively elucidates the hepatotoxicity and synergistic toxic effects of and its formulations XLGB and ZGGJ, offering a modern scientific rationale to guide the safe formulation and compatibility of traditional Chinese medicine.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-08
2026-01-29

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Deciphering the Key Toxicants and Hepatotoxicity Mechanisms of Epimedii Folium and its Preparations via Network Toxicology and Molecular Docking
Bentham Science Publishers ; https://doi.org/10.2174/0113862073440917251105054437
/content/journals/cchts/10.2174/0113862073440917251105054437
/content/journals/cchts/10.2174/0113862073440917251105054437
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  • Article Type:     Research Article
Keywords: hepatotoxicity ; Epimedii Folium ; xianling gubao capsule ; zhuanggu guanjie pill ; synergistic toxicity effect ; network toxicology

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