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Abstract

Introduction

Icaritin is a bioactive flavonol isolated from the Chinese medicinal herb . The comprehensive understanding of antifibrotic effects and associated molecular mechanisms of icaritin remains incomplete. This study aims to explore the protective effects of icaritin against liver fibrosis and to further elucidate the mechanisms involved.

Methods

Human hepatic stellate LX-2 cells stimulated with TGF-β1 and a carbon tetrachloride (CCl)-induced liver fibrosis mouse model were employed. assays were carried out to evaluate collagen type I (COL I) and α-smooth muscle actin (α-SMA) expression, while studies assessed fibrosis alleviation. Molecular mechanisms were explored analysis of TGF-β1, phosphorylated Smad2/3, and HIF-1α protein levels using Western blotting.

Results

Icaritin suppressed TGF-β1-induced COL I and α-SMA expression in LX-2 cells and ameliorated liver fibrosis in CCl-treated mice. Mechanistically, it significantly reduced TGF-β1 levels, inhibited Smad2/3 phosphorylation, and downregulated HIF-1α protein expression in LX-2 cells.

Conclusion

Icaritin attenuated experimental liver fibrosis through the inhibition of the TGF-β/Smad and HIF-1α signaling pathways, highlighting its therapeutic potential for fibrotic liver diseases.

© 2025 The Author(s).
© 2025 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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2025-05-05
2025-09-08

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Icaritin Attenuates HSC Activation by Down-regulating the HIF-1α and TGF-β/Smad Signaling Pathways to Ameliorate Liver Fibrosis
Bentham Science Publishers ; https://doi.org/10.2174/0109298673362768250417052953
/content/journals/cmc/10.2174/0109298673362768250417052953
/content/journals/cmc/10.2174/0109298673362768250417052953
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  • Article Type:     Research Article
Keywords: hepatic stellate cell (HSC) activation ; antifibrotic therapy ; HIF-1α ; Icaritin ; TGF-β/Smad ; liver fibrosis

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