title: Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus.
abstract: Salidroside (SAL) is an active ingredient isolated from the Rhodiola rosea, has potent anti-inflammatory effect, but the mechanism is still elusive. The purpose of this study is to verify the effects of SAL on LPS-induced inflammatory response and investigate the possible underlying molecular mechanism. RAW264.7 cells were pre-incubated with SAL for 2h, then stimulated with or without LPS for another 16h. The levels of TNF-α, MCP-1, IL-6, and PGE2 were detected by ELISA, and the production of NO was determined by nitrite analysis. The expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blotting. In RAW264.7 cells and murine peritoneal macrophages, the activation of signal molecules was also measured by Western blot. The nuclear translocation of STAT3 was determined by Laser confocal and nucleocytoplasmic separation experiments. Our results showed that SAL attenuated the productions of TNF-α, IL-6, MCP-1, PGE2 and NO dose dependently. SAL also suppressed LPS-induced expressions of iNOS and COX-2 significantly. Further studies revealed that SAL down-regulated the phosphorylation of JAK2-STAT3 signaling pathway and reduced the nuclear translocation of STAT3 induced by LPS in RAW264.7 cells and primary peritoneal macrophages. In addition, consistent with the results in vitro, in the model of mice acute lung injury (ALI) induced by LPS, SAL reduced the infiltration of inflammatory cells and decreased the levels of serum TNF-α and IL-6 obviously. Taken together, these data indicated that SAL exerted anti-inflammatory action via down-regulating LPS-induced activation of JAK2-STAT3 pathway and suppressing STAT3 transfer into the nucleus at least in part.
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, China; Anhui Province Key Laboratory of Active Biological Macro-molecules, Wuhu, Anhui, China. Electronic address: 422627721@qq.com.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, China; Anhui Province Key Laboratory of Active Biological Macro-molecules, Wuhu, Anhui, China.
authors.forename: Shimei
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, China; Anhui Province Key Laboratory of Active Biological Macro-molecules, Wuhu, Anhui, China.
authors.forename: Liefeng
authors.initials: L
authors.lastname: Ling
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, China; Anhui Province Key Laboratory of Active Biological Macro-molecules, Wuhu, Anhui, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lv
authors.affiliation: Anhui Province Key Laboratory of Active Biological Macro-molecules, Wuhu, Anhui, China.
authors.forename: Zunyong
authors.initials: Z
authors.lastname: Feng
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005960:Glucosides / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D005960:Glucosides; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010636:Phenols; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D052247:Nitric Oxide Synthase Type II; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; C009172:rhodioloside
keywords: Acute lung injury; Inflammation; JAK2-STAT3; LPS; Salidroside