Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways

Objective. The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice. Methods. Carbon tetrachloride (CCl4) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver...

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Main Authors: Jie Ji, Qiang Yu, Weiqi Dai, Liwei Wu, Jiao Feng, Yuanyuan Zheng, Yan Li, Chuanyong Guo
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2021/6651839
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author Jie Ji
Qiang Yu
Weiqi Dai
Liwei Wu
Jiao Feng
Yuanyuan Zheng
Yan Li
Chuanyong Guo
author_facet Jie Ji
Qiang Yu
Weiqi Dai
Liwei Wu
Jiao Feng
Yuanyuan Zheng
Yan Li
Chuanyong Guo
author_sort Jie Ji
collection DOAJ
description Objective. The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice. Methods. Carbon tetrachloride (CCl4) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver fibrosis. Sixty-six male C57 mice were randomly divided into eight groups, including the vehicle group, CCl4 group, CCl4+L-apigenin (20 mg/kg) group, CCl4+H-apigenin (40 mg/kg) group, sham group, BDL group, BDL+L-apigenin(20 mg/kg) group, and BDL+H-apigenin(40 mg/kg) group. Serum liver enzymes (ALT and AST), proteins associated with autophagy, and indicators linked with the TGF-β1/Smad3 and p38/PPARα pathways were detected using qRT-PCR, immunohistochemical staining, and western blotting. Results. Our findings confirmed that apigenin could decrease the levels of ALT and AST, suppress the generation of ECM, inhibit the activation of HSCs, regulate the balance of MMP2 and TIMP1, reduce the expression of autophagy-linked protein, and restrain the TGF-β1/Smad3 and p38/PPARα pathways. Conclusion. Apigenin could alleviate liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-β1/Smad3 and p38/PPARα pathways.
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spelling doaj-art-caa5b468d4914d2c94c53aaeac29996c2025-08-20T02:19:37ZengWileyPPAR Research1687-47571687-47652021-01-01202110.1155/2021/66518396651839Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα PathwaysJie Ji0Qiang Yu1Weiqi Dai2Liwei Wu3Jiao Feng4Yuanyuan Zheng5Yan Li6Chuanyong Guo7Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaObjective. The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice. Methods. Carbon tetrachloride (CCl4) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver fibrosis. Sixty-six male C57 mice were randomly divided into eight groups, including the vehicle group, CCl4 group, CCl4+L-apigenin (20 mg/kg) group, CCl4+H-apigenin (40 mg/kg) group, sham group, BDL group, BDL+L-apigenin(20 mg/kg) group, and BDL+H-apigenin(40 mg/kg) group. Serum liver enzymes (ALT and AST), proteins associated with autophagy, and indicators linked with the TGF-β1/Smad3 and p38/PPARα pathways were detected using qRT-PCR, immunohistochemical staining, and western blotting. Results. Our findings confirmed that apigenin could decrease the levels of ALT and AST, suppress the generation of ECM, inhibit the activation of HSCs, regulate the balance of MMP2 and TIMP1, reduce the expression of autophagy-linked protein, and restrain the TGF-β1/Smad3 and p38/PPARα pathways. Conclusion. Apigenin could alleviate liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-β1/Smad3 and p38/PPARα pathways.http://dx.doi.org/10.1155/2021/6651839
spellingShingle Jie Ji
Qiang Yu
Weiqi Dai
Liwei Wu
Jiao Feng
Yuanyuan Zheng
Yan Li
Chuanyong Guo
Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
PPAR Research
title Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
title_full Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
title_fullStr Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
title_full_unstemmed Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
title_short Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways
title_sort apigenin alleviates liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via tgf β1 smad3 and p38 pparα pathways
url http://dx.doi.org/10.1155/2021/6651839
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