Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway
Objective: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. Methods: The hepatoprotective effects...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223008880 |
| _version_ | 1797744103655473152 |
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| author | Laiyu Zhu Xiaoye Fan Chunyuan Cao Kailiang Li Wenli Hou Xinxin Ci |
| author_facet | Laiyu Zhu Xiaoye Fan Chunyuan Cao Kailiang Li Wenli Hou Xinxin Ci |
| author_sort | Laiyu Zhu |
| collection | DOAJ |
| description | Objective: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. Methods: The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately. Results: In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3β pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3β phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated. Conclusion: Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3β/Nrf2 antioxidant pathway. |
| first_indexed | 2024-03-12T15:05:54Z |
| format | Article |
| id | doaj.art-fc5d301805464f1cbab655d41323176f |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:05:54Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-fc5d301805464f1cbab655d41323176f2023-08-13T04:52:34ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115097Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathwayLaiyu Zhu0Xiaoye Fan1Chunyuan Cao2Kailiang Li3Wenli Hou4Xinxin Ci5Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, ChinaInstitute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Jilin Province People's Hospital, Changzhun, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Jilin Province People's Hospital, Changzhun, ChinaDepartment of Cadre Ward, the First Hospital of Jilin University, 71 Xinmin Street, Chaoyang, Changchun, Jilin 130021, China; Corresponding authors.Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, China; Corresponding authors.Objective: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. Methods: The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately. Results: In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3β pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3β phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated. Conclusion: Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3β/Nrf2 antioxidant pathway.http://www.sciencedirect.com/science/article/pii/S0753332223008880AcetaminophenHepatotoxicityOxidative stressXanthohumolNrf2 |
| spellingShingle | Laiyu Zhu Xiaoye Fan Chunyuan Cao Kailiang Li Wenli Hou Xinxin Ci Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway Biomedicine & Pharmacotherapy Acetaminophen Hepatotoxicity Oxidative stress Xanthohumol Nrf2 |
| title | Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway |
| title_full | Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway |
| title_fullStr | Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway |
| title_full_unstemmed | Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway |
| title_short | Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway |
| title_sort | xanthohumol protect against acetaminophen induced hepatotoxicity via nrf2 activation through the ampk akt gsk3β pathway |
| topic | Acetaminophen Hepatotoxicity Oxidative stress Xanthohumol Nrf2 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223008880 |
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