Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury.
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 and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. 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.
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. sunpeng3001@aliyun.com.|Clinical Research Center, Yanbian University Hospital, Yanji 133002, China. sunpeng3001@aliyun.com.
Peng
P
Sun
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. szsong@ybu.edu.cn.
Shun-Zong
SZ
Song
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. 2014001052@ybu.edu.cn.
Shuang
S
Jiang
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. lixiawo@163.com.
Xia
X
Li
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. 2015001055@ybu.edu.cn.
You-Li
YL
Yao
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. ylwu@ybu.edu.cn.
Yan-Ling
YL
Wu
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. lhlian@ybu.edu.cn.
Li-Hua
LH
Lian
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. jxnan@ybu.edu.cn.|Clinical Research Center, Yanbian University Hospital, Yanji 133002, China. jxnan@ybu.edu.cn.
Ji-Xing
JX
Nan
D000818:Animals; D063425:Binge Drinking / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005960:Glucosides / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000633:toxicity; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D010636:Phenols / Q000493:pharmacokinetics*; D000067996:RAW 264.7 Cells; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
D051546:Cyclooxygenase 2; D005960:Glucosides; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D010636:Phenols; D051197:Toll-Like Receptor 4; D000099151:MAP Kinase Kinase Kinase 7; C493487:Tlr4 protein, mouse; C077623:Ptgs2 protein, mouse; C009172:rhodioloside
TAK1; TLR4; alcoholic liver injury; inflammation; salidroside