Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1.

Abstract

Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.

• Authors: Kuo-Cheng Lan, Sung-Chuan Chao, Hsiao-Yi Wu, Chia-Lien Chiang, Ching-Chia Wang, Shing-Hwa Liu, Te-I Weng
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 12026 (09 20 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28931916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosides
• HMGB1 Protein
• NF-kappa B
• Phenols
• Sirtuin 1
• rhodioloside

Topics

• Acute Lung Injury (etiology, metabolism, prevention & control)
• Animals
• Down-Regulation (drug effects)
• Glucosides (pharmacology)
• HMGB1 Protein (metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• NF-kappa B (metabolism)
• Phenols (pharmacology)
• Phytotherapy
• RAW 264.7 Cells
• Rhodiola (chemistry)
• Sepsis (complications)
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Up-Regulation (drug effects)