title: Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.
abstract: Biochanin A, an isoflavone existed in red clover and peanuts, has been reported to possess a wide spectrum of pharmacological activities, such as anti-inflammatory and antioxidant effects. However, the protective effects and mechanism of biochanin A on liver injury have not been reported. In this study, acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (D-GalN). Biochanin A was administrated 1h prior to LPS/D-GalN challenge. Serum ALT, AST, IL-1β, and TNF-α levels, hepatic malondialdehyde (MDA), GPx, SOD, and Catalase contents, tissue histology, IL-1β, TNF-α, NLRP3, and Nrf2 expression were detected. The results showed that serum ALT, AST, IL-1β, and TNF-α levels and hepatic MDA content increased after LPS/GalN treatment. These changes were attenuated by biochanin A. Meanwhile, biochanin A dose-dependently up-regulated the expression of Nrf2 and HO-1. Biochanin A also inhibited hepatic IL-1β and TNF-α expression in a dose-dependent manner. Biochanin A did not inhibit LPS/D-GalN-induced hepatic NLRP3, ASC, and caspase-1 expression. However, the interaction of NLRP3 with ASC and caspase-1 were inhibited by biochanin A. In addition, LPS/D-GalN-induced up-regulation of thioredoxin-interacting protein (TXNIP) and interaction between TXNIP and NLRP3 were also inhibited by biochanin A. In conclusion, biochanin A protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital, Jilin University, Changchun 130021, China. Electronic address: liuxingkailx@sina.com.
authors.forename: Xingkai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hospital Administration of Jilin University, Changchun 130021, China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second hospital, Jilin University, Changchun 130041, China.
authors.forename: Xueshibojie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, KY 40202, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital, Jilin University, Changchun 130021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital, Jilin University, Changchun 130021, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Surgery, School of Medicine, University of Louisville, KY 40202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology; D005688:Galactosamine / Q000276:immunology; D019833:Genistein / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C495636:Nfe2l2 protein, mouse; C492716:Nlrp3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C445672:Txnip protein, mouse; D013879:Thioredoxins; D005688:Galactosamine; D019833:Genistein; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C004541:biochanin A
keywords: Biochanin A; LPS; NLRP3; Nrf2; TXNIP