title: 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.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China. linhongli@vip.163.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China. wutaihua@sina.com.
authors.forename: Taihua
authors.initials: T
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D001761:Bleomycin; D002460:Cell Line; D005960:Glucosides / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D010636:Phenols / Q000737:chemistry / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017207:Rats, Sprague-Dawley; D029771:Rhodiola / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000276:immunology; D051900:Smad3 Protein / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005960:Glucosides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D010636:Phenols; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; C009172:rhodioloside
keywords: EMT; NF-κB p65 signaling pathway; Nrf2 signaling pathway; Pulmonary fibrosis; Salidroside; TGF-β1/Smad2/3 signaling pathway