title: Schisantherin A protects against liver ischemia-reperfusion injury via inhibition of mitogen-activated protein kinase pathway.
abstract: Schisantherin A (SchA) is a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera. The role of SchA in liver injury induced by ischemia and reperfusion (I/R) has not yet been elucidated. The present study hypothesized the protective effects of SchA in hepatic I/R model. Either sham laparotomy or hepatic I/R was induced in C57BL/6 male mice after SchA or vehicle administration. Liver function, histological damage, oxidative/nitrosative stress, inflammatory infiltration, cytokine production, cell apoptosis, cell autophagy, and I/R-associated intracellular signaling pathway were assessed to evaluate the impact of SchA pretreatment on I/R-induced liver injury. After liver I/R injury, the mice pretreated with appropriate SchA displayed significantly preserved liver function, less histological damage, ameliorated oxidative/nitrosative stress, attenuated inflammatory state, and reduced cell apoptosis. However, no differences in the autophagic response were detected after SchA pretreatment. The underlying protective mechanism putatively involves the inhibition of mitogen-activated protein kinase (MAPK) signaling pathway. Based on the beneficial effects, SchA pretreatment may serve as a potential prophylactic measure to prevent liver I/R injury related to various clinical conditions.
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: guowenyuan@medmail.com.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: dingguoshanmail@163.com.
authors.forename: Guoshan
authors.initials: G
authors.lastname: Ding
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D034242:Cyclooctanes / Q000627:therapeutic use*; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*; D029633:Schisandraceae / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; C034557:schizandrer A; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cellular apoptosis; Cellular autophagy; Inflammatory state; Liver ischemia reperfusion; Oxidative/nitrosative stress; Schisantherin A