Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis

Abstract Astragaloside IV (AST-IV), as one of the main functional components of Astragalus membranaceus, has physiological functions such as regulating metabolism and anti-tumor. However, the role of AST-IV on hepatocellular carcinoma (HCC) was still poorly understood. In this study, our work explor...

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Main Authors: Xingyang Zhao, Ruizhe Liu, Haiyu Zhou, Deqing Wu
Format: Article
Language:English
Published: Springer 2025-08-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03286-5
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author Xingyang Zhao
Ruizhe Liu
Haiyu Zhou
Deqing Wu
author_facet Xingyang Zhao
Ruizhe Liu
Haiyu Zhou
Deqing Wu
author_sort Xingyang Zhao
collection DOAJ
description Abstract Astragaloside IV (AST-IV), as one of the main functional components of Astragalus membranaceus, has physiological functions such as regulating metabolism and anti-tumor. However, the role of AST-IV on hepatocellular carcinoma (HCC) was still poorly understood. In this study, our work explored whether AST-IV could induce ferroptosis and repress HCC tumorigenesis. Results indicated that AST-IV could repress the tumor progression (viability, migration) of HCC in vitro. Besides, AST-IV induced the ferroptosis (Fe2+, malondialdehyde, lipid peroxidation) in HCC cells. Molecular docking and microscale thermophoresis indicated that high mobility group protein B1 (HMGB1) acted as the target of AST-IV. AST-IV could repress the HMGB1 expression and HMGB1 reversed the role of AST-IV on HCC cells’ ferroptosis. In vivo, AST-IV administration repressed the tumor progression. In conclusion, AST-IV represses HCC progression by modulating HMGB1-ferroptosis axis, which provides a novel insight for HCC.
format Article
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institution Kabale University
issn 2730-6011
language English
publishDate 2025-08-01
publisher Springer
record_format Article
series Discover Oncology
spelling doaj-art-9957a2a1925b4af3ba97174ae211aa012025-08-20T03:46:17ZengSpringerDiscover Oncology2730-60112025-08-0116111110.1007/s12672-025-03286-5Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axisXingyang Zhao0Ruizhe Liu1Haiyu Zhou2Deqing Wu3Department of General Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital Ganzhou Hospital, Guangdong Academy of Medical SciencesDepartment of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical SciencesDepartment of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical SciencesDepartment of General Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital Ganzhou Hospital, Guangdong Academy of Medical SciencesAbstract Astragaloside IV (AST-IV), as one of the main functional components of Astragalus membranaceus, has physiological functions such as regulating metabolism and anti-tumor. However, the role of AST-IV on hepatocellular carcinoma (HCC) was still poorly understood. In this study, our work explored whether AST-IV could induce ferroptosis and repress HCC tumorigenesis. Results indicated that AST-IV could repress the tumor progression (viability, migration) of HCC in vitro. Besides, AST-IV induced the ferroptosis (Fe2+, malondialdehyde, lipid peroxidation) in HCC cells. Molecular docking and microscale thermophoresis indicated that high mobility group protein B1 (HMGB1) acted as the target of AST-IV. AST-IV could repress the HMGB1 expression and HMGB1 reversed the role of AST-IV on HCC cells’ ferroptosis. In vivo, AST-IV administration repressed the tumor progression. In conclusion, AST-IV represses HCC progression by modulating HMGB1-ferroptosis axis, which provides a novel insight for HCC.https://doi.org/10.1007/s12672-025-03286-5Astragaloside IVHepatocellular carcinomaHMGB1Ferroptosis
spellingShingle Xingyang Zhao
Ruizhe Liu
Haiyu Zhou
Deqing Wu
Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
Discover Oncology
Astragaloside IV
Hepatocellular carcinoma
HMGB1
Ferroptosis
title Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
title_full Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
title_fullStr Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
title_full_unstemmed Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
title_short Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis
title_sort astragaloside iv represses hepatocellular carcinoma progression by modulating hmgb1 ferroptosis axis
topic Astragaloside IV
Hepatocellular carcinoma
HMGB1
Ferroptosis
url https://doi.org/10.1007/s12672-025-03286-5
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AT ruizheliu astragalosideivrepresseshepatocellularcarcinomaprogressionbymodulatinghmgb1ferroptosisaxis
AT haiyuzhou astragalosideivrepresseshepatocellularcarcinomaprogressionbymodulatinghmgb1ferroptosisaxis
AT deqingwu astragalosideivrepresseshepatocellularcarcinomaprogressionbymodulatinghmgb1ferroptosisaxis