title: New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats.
abstract: Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury, and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS, and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation, and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways.
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: 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: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Zu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Zhenlu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Zhou
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.
authors.forename: Li
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000475:Alkenes; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004041:Dietary Fats; C442825:Mlxipl protein, rat; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D059808:Polyphenols; C493796:TXNIP protein, rat; C568740:salvianolic acid