title: Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.
abstract: Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Chen-wei
authors.initials: CW
authors.lastname: Pan
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.
authors.forename: Zhen-zhen
authors.initials: ZZ
authors.lastname: Pan
authors.affiliation: Intensive Care Unit, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Jian-jian
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Department of Neurology, Wenzhou People's Hospital, Wenzhou 325027, PR China.
authors.forename: Wei-lai
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Guang-yao
authors.initials: GY
authors.lastname: Zhou
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Ling-xiang
authors.initials: LX
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China. Electronic address: xuchanglongyl@163.com.
authors.forename: Chang-long
authors.initials: CL
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002352:Carrier Proteins / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D019610:Cytoprotection / Q000187:drug effects; D005688:Galactosamine / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D058847:Inflammasomes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D044004:Xanthones; C013592:mangiferin; D008315:Malondialdehyde; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: LPS; Mangiferin; NLRP3; Nrf2