Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling
Cardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the prot...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.601716/full |
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| author | Qiushi Xu Yunhui Fan Juan J. Loor Yusheng Liang Xudong Sun Hongdou Jia Chenxu Zhao Chuang Xu |
| author_facet | Qiushi Xu Yunhui Fan Juan J. Loor Yusheng Liang Xudong Sun Hongdou Jia Chenxu Zhao Chuang Xu |
| author_sort | Qiushi Xu |
| collection | DOAJ |
| description | Cardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the protective effects of CD against APAP-induced acute liver injury (ALI) and the underlying mechanisms. Wild-type or transcription factor nuclear factor erythroid 2-related factor 2- (NFE2L2-) deficient mice were treated with CD (50 or 100 mg/kg, i.p.) or vehicle for 24 h. Subsequently, these mice were challenged with APAP (400 mg/kg, i.p.) for 6 h. Liver and blood samples were collected to evaluate liver injury and protein abundance. Treatment with CD significantly reduced APAP-induced hepatotoxicity. Furthermore, CD effectively reduced APAP-induced inflammation by inhibiting high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and NOD-like receptor protein 3 (NLRP3) signaling. In addition, CD induced activation of sequestosome 1 (p62) and NFE2L2 signaling and facilitated autophagy. By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2−/− mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy. |
| first_indexed | 2024-12-23T04:19:45Z |
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| language | English |
| last_indexed | 2024-12-23T04:19:45Z |
| publishDate | 2020-11-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-7dc3dc8a1a0949c28b0ac567852cbe0c2022-12-21T18:00:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.601716601716Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 SignalingQiushi Xu0Yunhui Fan1Juan J. Loor2Yusheng Liang3Xudong Sun4Hongdou Jia5Chenxu Zhao6Chuang Xu7College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaMammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United StatesMammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United StatesCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the protective effects of CD against APAP-induced acute liver injury (ALI) and the underlying mechanisms. Wild-type or transcription factor nuclear factor erythroid 2-related factor 2- (NFE2L2-) deficient mice were treated with CD (50 or 100 mg/kg, i.p.) or vehicle for 24 h. Subsequently, these mice were challenged with APAP (400 mg/kg, i.p.) for 6 h. Liver and blood samples were collected to evaluate liver injury and protein abundance. Treatment with CD significantly reduced APAP-induced hepatotoxicity. Furthermore, CD effectively reduced APAP-induced inflammation by inhibiting high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and NOD-like receptor protein 3 (NLRP3) signaling. In addition, CD induced activation of sequestosome 1 (p62) and NFE2L2 signaling and facilitated autophagy. By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2−/− mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy.https://www.frontiersin.org/articles/10.3389/fphar.2020.601716/fullcardamoninacetaminophenacute liver injuryautophagyNFE2L2 |
| spellingShingle | Qiushi Xu Yunhui Fan Juan J. Loor Yusheng Liang Xudong Sun Hongdou Jia Chenxu Zhao Chuang Xu Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling Frontiers in Pharmacology cardamonin acetaminophen acute liver injury autophagy NFE2L2 |
| title | Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling |
| title_full | Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling |
| title_fullStr | Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling |
| title_full_unstemmed | Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling |
| title_short | Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling |
| title_sort | cardamonin reduces acetaminophen induced acute liver injury in mice via activating autophagy and nfe2l2 signaling |
| topic | cardamonin acetaminophen acute liver injury autophagy NFE2L2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.601716/full |
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