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Int. J. Mol. Sci. 2016, 17(6), 879; doi:10.3390/ijms17060879

Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats

1
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
2
Shihezi Institute for Drug Control, Shihezi 832002, China
3
College of Pharmacy, Shihezi University, Shihezi 832002, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 30 March 2016 / Revised: 15 May 2016 / Accepted: 24 May 2016 / Published: 3 June 2016
(This article belongs to the Section Bioactives and Nutraceuticals)
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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. View Full-Text
Keywords: Rhodiola rosea L.; pulmonary fibrosis; bleomycin; TGF-β1; MMP-9 Rhodiola rosea L.; pulmonary fibrosis; bleomycin; TGF-β1; MMP-9
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MDPI and ACS Style

Zhang, K.; Si, X.-P.; Huang, J.; Han, J.; Liang, X.; Xu, X.-B.; Wang, Y.-T.; Li, G.-Y.; Wang, H.-Y.; Wang, J.-H. Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats. Int. J. Mol. Sci. 2016, 17, 879.

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