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

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.

Salidroside Attenuates Ventilation Induced Lung Injury via SIRT1-Dependent Inhibition of NLRP3 Inflammasome

“…It is of interest that salidroside has been demonstrated to have protective effects against pulmonary fibrosis. Tang et al demonstrate that in bleomycin-induced pulmonary fibrosis salidroside can inhibit IκBα phosphorylation and nuclear factor kappa B (NF-κB) via activating Nrf2-antioxidant signaling [25]. The recombinant TGF-β1-induced EMT-like changes can be reversed and the expression of TGF-β1 and the phosphorylation of its downstream targets, Smad-2/-3, were weakened by salidroside.…”

Rhodiola rosea L.: an Herb with Anti-Stress, Anti-Aging, and Immunostimulating Properties for Cancer Chemoprevention

“…In addition, Rhodiola rosea extracts and salidroside was able to increase the expression of antioxidant enzymes (e.g. GPx) and activate the nuclear erythroid 2-related factor 2 (Nrf2) pathways in rats to protect against bleomycin-induced pulmonary fibrosis in rats [68] and to reverse ultraviolet B induced DNA damages in HaCaT cells [69], respectively.…”

Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

“…It was seen that salidroside could protect against epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer . Surprisingly, salidroside has also been reported to protect against PF in a recent work (Tang et al, 2016). It was reported that salidroside attenuated BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, and pro-inflammatory cytokine release, and oxidative stress damages in lung tissues (Tang et al, 2016).…”

“…-SD rats (BLM, 7.5 U/kg) Tang et al (2016) Astragalin Diospyros kaki L.f. -Wistar rats (BLM, 2.5 mg/kg), ICR mice (LPS, 5 mg/kg) - Akgedik et al (2012) and Zhang et al (2015) Curcumin Curcuma longa L. PMVEC, primary FB (IR, 2 Gy) C57BL/6 mice (0.5 μg LPS or 13.5 Gy IR), CBA/J mice (reovirus 1/L, 10 7 PFU) FB (TGF-β, 6 ng/ml), PF patients Lee et al (2010), Smith et al (2010), Avasarala et al (2013) and Jiang and Zhang (2015a) EGCG Camellia sinensis (L.) Kuntze FB WI−38 (TGF-β1, 10 ng/ml) Wistar rats (BLM, 6.5 U/kg), SD rats (IR, 22 Gy) - Sriram et al (2009aSriram et al ( , 2009bSriram et al ( , 2015 and You et al (2014) Corilagin Caesalpinia coriaria (Jacq. )…”