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Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice.
Oxid Med Cell Longev. 2018; 2018:8284107.OM

Abstract

Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.

Authors+Show Affiliations

Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.Department of Animal Medicine, Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30344887

Citation

Xu, Lu, et al. "Protective Effects of Taraxasterol Against Ethanol-Induced Liver Injury By Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice." Oxidative Medicine and Cellular Longevity, vol. 2018, 2018, p. 8284107.
Xu L, Yu Y, Sang R, et al. Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice. Oxid Med Cell Longev. 2018;2018:8284107.
Xu, L., Yu, Y., Sang, R., Li, J., Ge, B., & Zhang, X. (2018). Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice. Oxidative Medicine and Cellular Longevity, 2018, 8284107. https://doi.org/10.1155/2018/8284107
Xu L, et al. Protective Effects of Taraxasterol Against Ethanol-Induced Liver Injury By Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice. Oxid Med Cell Longev. 2018;2018:8284107. PubMed PMID: 30344887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice. AU - Xu,Lu, AU - Yu,Yifan, AU - Sang,Rui, AU - Li,Jinxia, AU - Ge,Bingjie, AU - Zhang,Xuemei, Y1 - 2018/09/23/ PY - 2018/06/26/received PY - 2018/08/07/revised PY - 2018/08/15/accepted PY - 2018/10/23/entrez PY - 2018/10/23/pubmed PY - 2018/11/27/medline SP - 8284107 EP - 8284107 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2018 N2 - Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/30344887/Protective_Effects_of_Taraxasterol_against_Ethanol_Induced_Liver_Injury_by_Regulating_CYP2E1/Nrf2/HO_1_and_NF_κB_Signaling_Pathways_in_Mice_ L2 - https://doi.org/10.1155/2018/8284107 DB - PRIME DP - Unbound Medicine ER -