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Cell Stress and Chaperones

, Volume 21, Issue 2, pp 239–249 | Cite as

Salidroside protects against bleomycin-induced pulmonary fibrosis: activation of Nrf2-antioxidant signaling, and inhibition of NF-κB and TGF-β1/Smad-2/-3 pathways

  • Haiying Tang
  • Lili Gao
  • Jingwei Mao
  • Huanyu He
  • Jia Liu
  • Xin Cai
  • Hongli LinEmail author
  • Taihua WuEmail author
Original Paper

Abstract

Pulmonary fibrosis (PF) can severely disrupt lung function, leading to fatal consequences. Salidroside is a principal active ingredient of Rhodiola rosea and has recently been reported to protect against lung injures. The present study was aimed at exploring its therapeutic effects on PF. Lung fibrotic injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administrated with 50, 100, or 200 mg/kg salidroside for 28 days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, and pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated by salidroside in a dose-dependent manner. Furthermore, salidroside was noted to inhibit IκBα phosphorylation and nuclear factor kappa B (NF-κB) p65 nuclear accumulation while activating Nrf2-antioxidant signaling in BLM-treated lungs. Downregulation of E-cadherin and upregulation of vimentin, fibronectin, and α-smooth muscle actin (α-SMA) indicated an epithelial-mesenchymal transition (EMT)-like shift in BLM-treated lungs. These changes were suppressed by salidroside. The expression of TGF-β1 and the phosphorylation of its downstream targets, Smad-2/-3, were enhanced by BLM, but weakened by salidroside. Additionally, salidroside was capable of reversing the recombinant TGF-β1-induced EMT-like changes in alveolar epithelial cells in vitro. Our study reveals that salidroside’s protective effects against fibrotic lung injuries are correlated to its anti-inflammatory, antioxidative, and antifibrotic properties.

Keywords

Salidroside Pulmonary fibrosis EMT NF-κB p65 signaling pathway Nrf2 signaling pathway TGF-β1/Smad2/3 signaling pathway 

Notes

Acknowledgments

This study was supported by grants from the National Nature Science Foundation of China (No. 81273924) and the Nature Science Foundation of Liaoning Province (No. 2013023028).

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Copyright information

© Cell Stress Society International 2015

Authors and Affiliations

  1. 1.Department of Respiratory MedicineThe First Affiliated Hospital of Dalian Medical UniversityDalianPeople’s Republic of China
  2. 2.Department of GastroenterologyThe First Affiliated Hospital of Dalian Medical UniversityDalianPeople’s Republic of China
  3. 3.Department of OncologyThe First Affiliated Hospital of Dalian Medical UniversityDalianPeople’s Republic of China
  4. 4.Department of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianPeople’s Republic of China

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