Abstract
Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague–Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T-SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-β1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-β1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play important roles in BLM-induced PF.
Highlights
Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive proliferation of fibroblasts and deposition of collagens and other extracellular matrix (ECM) proteins [1]
PF is induced by a variety of etiological factors, including inflammation, the epithelial–mesenchymal transition (EMT), oxidative stress, and immune dysfunction, which result in alveolar epithelial cell injury, and fibroblast proliferation that lead to abnormal deposition of the extracellular matrix (ECM) and tissue remodeling
To determine the effect of Rhodiola rosea L. (RRL) on the BLM-induced pulmonary inflammatory response in rats, levels of the inflammatory cytokines transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and IL-6 were determined in bronchoalveolar lavage fluid (BALF)
Summary
Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive proliferation of fibroblasts and deposition of collagens and other extracellular matrix (ECM) proteins [1]. Many factors change the expression of MMPs, including pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which increase during the early phase of PF and are essential in the progression of early pulmonary inflammation to PF [4,5]. These changes have been associated with increased MMP levels [6] and induction of MMP production from various cell types, including alveolar epithelial cells, alveolar fibroblasts, and alveolar macrophages [7,8,9]. The PF mechanism is not completely understood, and novel therapeutic agents to treat PF are still needed
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