Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking Induced Liver Injury

Version 1 : Received: 27 September 2016 / Approved: 27 September 2016 / Online: 27 September 2016 (10:45:06 CEST)

A peer-reviewed article of this Preprint also exists.

Sun, P.; Song, S.-Z.; Jiang, S.; Li, X.; Yao, Y.-L.; Wu, Y.-L.; Lian, L.-H.; Nan, J.-X. Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury. Molecules 2016, 21, 1490. Sun, P.; Song, S.-Z.; Jiang, S.; Li, X.; Yao, Y.-L.; Wu, Y.-L.; Lian, L.-H.; Nan, J.-X. Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury. Molecules 2016, 21, 1490.

Abstract

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

Keywords

salidroside; inflammation; alcoholic liver injury; TLR4; TAK1

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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