Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.
In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future.
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Weixin
W
Zhang
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Lianhong
L
Yin
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Xufeng
X
Tao
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Lina
L
Xu
Department of Pharmaceuticals, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. Electronic address: zheng_ll2009@126.com.
Lingli
L
Zheng
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Xu
X
Han
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Youwei
Y
Xu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Changyuan
C
Wang
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2008@126.com.
Jinyong
J
Peng
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity*; D027742:Dioscorea / Q000737:chemistry; D004144:Diosgenin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D016207:Cytokines; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D053594:Myeloid Differentiation Factor 88; D051267:NF-E2-Related Factor 2; D051197:Toll-Like Receptor 4; C019357:dioscin; D056564:Sirtuin 1; D004144:Diosgenin; D004128:Dimethylnitrosamine
Apoptosis; DMN; Dioscin; Inflammation; Liver injury; Oxidative stress