title: Chinese Herbal Preparation Xuebijing Potently Inhibits Inflammasome Activation in Hepatocytes and Ameliorates Mouse Liver Ischemia-Reperfusion Injury.
abstract: The Chinese herb preparation Xuebijing injection (XBJ) has been widely used in the management of various septic disorders or inflammation-related conditions, however the molecular mechanism of its anti-inflammatory effect remains largely elusive. In the current study, we found that XBJ treatment potently ameliorated mouse hepatic ischemia-reperfusion (IR) injury, manifested as decreased liver function tests (LDH, ALT, AST), improved inflammation and less hepatocyte apoptosis. Notably, XBJ markedly inhibited inflammasome activation and IL-1 production in mouse livers subjected to IRI, even in the absence of Kupffer cells, suggesting Kupffer cells are not necessary for hepatic inflammasome activation upon Redox-induced sterile inflammation. This finding led us to investigate the role of XBJ on hepatocyte apoptosis and inflammasome activation using an in vitro hydrogen peroxide (H2O2)-triggered hepatocyte injury model. Our data clearly demonstrated that XBJ potently inhibited apoptosis, as well as caspase-1 cleavage and IL-1β production in a time- and dose-dependent manner in isolated hepatocytes, suggesting that in addition to its known modulatory effect on NF-κB-dependent inflammatory gene expression, it also has a direct impact on hepatocyte inflammasome activation. The current study not only deepens our understanding of how XBJ ameliorates inflammation and apoptosis, but also has immediate practical significance in many clinical situations such as partial hepatectomy, liver transplantation, etc.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Surgery, Minhang Hospital, Fudan University, Shanghai, PR China.
authors.forename: Zhiqiu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of cardiothoracic surgery, Zhejiang Provincial People's Hospital (ZJPPH), Hangzhou, Zhejiang Province, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Faculty of Basic Medicine, Zhejiang Medical College, Hangzhou, Zhejiang Province, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Provincial People's Hospital (ZJPPH), Hangzhou, Zhejiang Province, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D022781:Hepatocytes / Q000187:drug effects*; D058847:Inflammasomes / Q000037:antagonists & inhibitors*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D004365:Drugs, Chinese Herbal; D058847:Inflammasomes; D017382:Reactive Oxygen Species; C549376:Xuebijing