title: The protective effect of Esculentoside A on experimental acute liver injury in mice.
abstract: Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl4) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl4 and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-α and cell death rate challenged by CCl4. Moreover, EsA treatment up-regulated PPAR-γ expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl4. In vivo, EsA prevented mice from CCl4-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-α, Interleukin (IL)-1β and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl4-induced phosphonated IkBalpha (P-IκB) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl4-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl4 and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-γ, NF-κB and ERK signal pathways.
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China; Number 73901 Troop of PLA, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: Xingtong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, 309th Hospital of PLA, Beijing, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: He
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Burn Surgery, the Second Military Medical University affiliated Changhai Hospital, Shanghai, China.
authors.forename: Zhaofan
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012844:Sincalide / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D012503:Saponins; C076297:esculentoside A; D009828:Oleanolic Acid; D002251:Carbon Tetrachloride; D012844:Sincalide