Aucubin inhibits hepatic stellate cell activation through stimulating Nrf2/Smad7 axis
Copyright © 2023. Published by Elsevier B.V..
AIM: Liver fibrosis may develop into end-stage liver disease if left unprevented. The study is attempting to identify a compound to ameliorate liver fibrosis progression with high efficiency and low toxicity, as well as to analyze its potential molecular mechanism.
METHODS: The drug screening was performed using human hepatic stellate cell line LX-2 for identifying the compound as collagen I inhibitor. Primary Human hepatic stellate cells and LX-2 cell line were used to detect the antifibrotic function activity and molecular mechanism analysis in vitro. The CCl4-induced mouse experimental model was used to measure the amelioration in liver fibrosis.
RESULTS: This study identified Aucubin, a natural compound, as a candidate for anti-liver fibrosis. Besides, Aucubin could inhibit the collagen I and α-SMA expressions in LX-2 cells and primary human hepatic stellate cells, as well as the cell proliferation. In terms of mechanism, Aucubin could upregulate Smad7 in hepatic stellate cells in a dose-dependent manner and block TGF-β signaling. We also found that Nrf2 might be a direct target for the action of Aucubin, whose activation was necessary for Smad7 upregulation. In an in-vivo mouse model, Aucubin efficiency ameliorated the progression of CCl4-induced liver fibrosis, and reduced the hepatic levels of collagen deposition, transaminase and inflammatory cytokines.
CONCLUSION: Capable of inhibiting the activation of hepatic stellate cells in vitro and in vivo, Aucubin may be a potential therapeutic candidate for liver fibrosis, which is dependent on the suppression of TGF-β signaling through stimulating Nrf2/Smad7 axis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:957 |
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| Enthalten in: |
European journal of pharmacology - 957(2023) vom: 15. Okt., Seite 176002 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shi, Xu [VerfasserIn] |
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| Links: |
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| Themen: |
2G52GS8UML |
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| Anmerkungen: |
Date Completed 22.09.2023 Date Revised 22.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2023.176002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361061099 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a AIM: Liver fibrosis may develop into end-stage liver disease if left unprevented. The study is attempting to identify a compound to ameliorate liver fibrosis progression with high efficiency and low toxicity, as well as to analyze its potential molecular mechanism | ||
| 520 | |a METHODS: The drug screening was performed using human hepatic stellate cell line LX-2 for identifying the compound as collagen I inhibitor. Primary Human hepatic stellate cells and LX-2 cell line were used to detect the antifibrotic function activity and molecular mechanism analysis in vitro. The CCl4-induced mouse experimental model was used to measure the amelioration in liver fibrosis | ||
| 520 | |a RESULTS: This study identified Aucubin, a natural compound, as a candidate for anti-liver fibrosis. Besides, Aucubin could inhibit the collagen I and α-SMA expressions in LX-2 cells and primary human hepatic stellate cells, as well as the cell proliferation. In terms of mechanism, Aucubin could upregulate Smad7 in hepatic stellate cells in a dose-dependent manner and block TGF-β signaling. We also found that Nrf2 might be a direct target for the action of Aucubin, whose activation was necessary for Smad7 upregulation. In an in-vivo mouse model, Aucubin efficiency ameliorated the progression of CCl4-induced liver fibrosis, and reduced the hepatic levels of collagen deposition, transaminase and inflammatory cytokines | ||
| 520 | |a CONCLUSION: Capable of inhibiting the activation of hepatic stellate cells in vitro and in vivo, Aucubin may be a potential therapeutic candidate for liver fibrosis, which is dependent on the suppression of TGF-β signaling through stimulating Nrf2/Smad7 axis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aucubin | |
| 650 | 4 | |a Liver fibrosis | |
| 650 | 4 | |a Nrf2/Smad7 axis | |
| 650 | 4 | |a TGF-β signaling | |
| 650 | 7 | |a aucubin |2 NLM | |
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| 650 | 7 | |a NF-E2-Related Factor 2 |2 NLM | |
| 650 | 7 | |a Collagen Type I |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Jiang, Wenyan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, XiaoGuang |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, HeMing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhongfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Ai, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, YuTong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, YingYu |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Ying |e verfasserin |4 aut | |
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