Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats.
Salvianolic acid B (SalB) is isolated from the traditional Chinese medical herb salvia miltiorrhiza. It has many biological and pharmaceutical activities. This study aimed to investigate the effect of SalB on acute ethanol-induced hepatic injury in rats and to explore the role of SIRT1 in this process. The results showed that pretreatment with SalB significantly reduced ethanol-induced elevation in aminotransferase activities, decreased hepatotoxic cytokine levels such as Interleukin-6 (IL-6), and increased the antioxidant enzyme activity. Moreover, SalB pretreatment reversed the increase in NF-κB, cleaved caspase-3 and decrease in B-cell lymphoma-extra large (Bcl-xL) caused by ethanol exposure. Importantly, SalB pretreatment significantly increased the expression of SIRT1, a NAD(+)-dependent deacetylase, whereas the increase in SIRT1 was accompanied by decreased acetyl-p53 expression. In HepG2 cells, SalB pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly increased the acetylation of p53, and blocked SalB-induced acetylation of p53 down-regulation. Collectively, this study indicated that SalB can alleviate acute ethanol-induced hepatocyte apoptosis through SIRT1-mediated deacetylation of p53 pathway.
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Mingzhu
M
Li
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Yang
Y
Lu
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Yan
Y
Hu
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Xiaohan
X
Zhai
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Wei
W
Xu
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Huirong
H
Jing
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Xiaofeng
X
Tian
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Yuan
Y
Lin
Department of Pharmacology, Dalian Medical University, Dalian 116044, China. Electronic address: gaody1975@163.com.
Dongyan
D
Gao
Department of Pharmacology, Dalian Medical University, Dalian 116044, China; Research Institute of Integrated Traditional and Western Medicine, Dalian Medical University, Dalian 116044, China. Electronic address: yaojihong65@hotmail.com.
Jihong
J
Yao
D000107:Acetylation; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D047468:Immunoprecipitation; D008099:Liver / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D053630:Depsides
D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D001572:Benzofurans; D002492:Central Nervous System Depressants; D016207:Cytokines; D000431:Ethanol; D005978:Glutathione; D008315:Malondialdehyde; D034741:RNA, Small Interfering; D056564:Sirtuin 1; D016159:Tumor Suppressor Protein p53; C076944:salvianolic acid B; D053630:Depsides; C488368:Sirt1 protein, rat
Ethanol; Liver injury; SIRT1; Salvianolic acid B; p53