Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices

Abstract Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision‐cut liver slices (PCLS). These...

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Main Authors: Ke Luo, Yana Geng, Dorenda Oosterhuis, Vincent E. deMeijer, Peter Olinga
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.16136
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author Ke Luo
Yana Geng
Dorenda Oosterhuis
Vincent E. deMeijer
Peter Olinga
author_facet Ke Luo
Yana Geng
Dorenda Oosterhuis
Vincent E. deMeijer
Peter Olinga
author_sort Ke Luo
collection DOAJ
description Abstract Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision‐cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking. In this study, PCLS prepared from male mouse liver tissue (mPCLS), healthy human liver tissue (hhPCLS), and cirrhotic human liver tissue (chPCLS) were cultured for 48 h with varying concentrations of the three compounds. Our findings indicate that NRG reduced collagen type 1 (COL1A1) expression in a concentration‐dependent manner in both mPCLS and chPCLS, decreased fibrosis‐related gene expression, and significantly lowered pro‐collagen type 1 (PCOL1A1) levels in the culture medium by 54 ± 21% (mPCLS) and 78 ± 35% (chPCLS). Furthermore, NRG effectively inhibited IL‐1β and TNF‐α in mPCLS and IL‐1β in chPCLS on both gene and protein levels. AA specifically reduced COL1A1 and PCOL1A1 in chPCLS, while ICA selectively downregulated Col1a1 and Acta2 gene expression in mPCLS. This study suggests NRG's potential as an effective antifibrotic agent, warranting further investigation into its mechanisms and therapeutic applications in liver fibrosis.
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spelling doaj-art-8f10d295a56a4da6913b78515ff2d49a2025-01-25T06:41:00ZengWileyPhysiological Reports2051-817X2024-11-011221n/an/a10.14814/phy2.16136Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slicesKe Luo0Yana Geng1Dorenda Oosterhuis2Vincent E. deMeijer3Peter Olinga4Department of Pharmaceutical Technology and Biopharmacy University of Groningen Groningen the NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy University of Groningen Groningen the NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy University of Groningen Groningen the NetherlandsDepartment of Surgery, University of Groningen University Medical Center Groningen Groningen the NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy University of Groningen Groningen the NetherlandsAbstract Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision‐cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking. In this study, PCLS prepared from male mouse liver tissue (mPCLS), healthy human liver tissue (hhPCLS), and cirrhotic human liver tissue (chPCLS) were cultured for 48 h with varying concentrations of the three compounds. Our findings indicate that NRG reduced collagen type 1 (COL1A1) expression in a concentration‐dependent manner in both mPCLS and chPCLS, decreased fibrosis‐related gene expression, and significantly lowered pro‐collagen type 1 (PCOL1A1) levels in the culture medium by 54 ± 21% (mPCLS) and 78 ± 35% (chPCLS). Furthermore, NRG effectively inhibited IL‐1β and TNF‐α in mPCLS and IL‐1β in chPCLS on both gene and protein levels. AA specifically reduced COL1A1 and PCOL1A1 in chPCLS, while ICA selectively downregulated Col1a1 and Acta2 gene expression in mPCLS. This study suggests NRG's potential as an effective antifibrotic agent, warranting further investigation into its mechanisms and therapeutic applications in liver fibrosis.https://doi.org/10.14814/phy2.16136inflammationliver fibrosisnatural productsprecision‐cut liver slices
spellingShingle Ke Luo
Yana Geng
Dorenda Oosterhuis
Vincent E. deMeijer
Peter Olinga
Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
Physiological Reports
inflammation
liver fibrosis
natural products
precision‐cut liver slices
title Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
title_full Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
title_fullStr Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
title_full_unstemmed Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
title_short Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision‐cut liver slices
title_sort evaluating the antifibrotic potential of naringenin asiatic acid and icariin using murine and human precision cut liver slices
topic inflammation
liver fibrosis
natural products
precision‐cut liver slices
url https://doi.org/10.14814/phy2.16136
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