title: Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats.
abstract: Salvianolic acid B (SalB), a water-soluble polyphenol extracted from Radix Salvia miltiorrhiza, has been reported to possess many pharmacological activities. This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol-induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Importantly, SalB pretreatment significantly increased the expression of SIRT1 and downregulated the expression of inflammatory mediator C-reactive protein (CRP) and lipoprotein carbohydrate response element-binding protein (ChREBP). In vitro, SalB significantly reversed ethanol-induced down-regulation of SIRT1 and increased CRP and ChREBP expression. Interestingly, the effects of SalB on SIRT1, CRP and ChREBP were mostly abolished by treatment with either SIRT1 siRNA or EX527, a specific inhibitor of SIRT1, indicating that SalB decreased CRP and ChREBP expression by activating SIRT1. SalB exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression.
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China; Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, 116027, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, 116027, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shan
authors.affiliation: Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, 116027, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China. Electronic address: yaojihong65@hotmail.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D001572:Benzofurans / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D053630:Depsides
chemical_list: D000893:Anti-Inflammatory Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001572:Benzofurans; D015415:Biomarkers; D002227:Carbazoles; D002352:Carrier Proteins; D016207:Cytokines; D051538:Hepatocyte Nuclear Factor 1-alpha; D056572:Histone Deacetylase Inhibitors; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D056564:Sirtuin 1; C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; C030929:Crp protein, rat; C496487:HNF1A protein, human; C442825:Mlxipl protein, rat; C076944:salvianolic acid B; D053630:Depsides; C447939:SIRT1 protein, human; C488368:Sirt1 protein, rat
keywords: Alcoholic liver injury; CRP; ChREBP; SIRT1; Salvianolic acid B