Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats.
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.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. xjzk1984@163.com.
Ke
K
Zhang
Shihezi Institute for Drug Control, Shihezi 832002, China. shz_yjs@sina.com.
Xiao-Ping
XP
Si
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. profhj@163.com.
Jian
J
Huang
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. 13998302950@163.com.
Jian
J
Han
College of Pharmacy, Shihezi University, Shihezi 832002, China. lix8182@163.com.
Xu
X
Liang
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. xxb517234556@sina.com.
Xiao-Bo
XB
Xu
College of Pharmacy, Shihezi University, Shihezi 832002, China. christina.wyt@foxmail.com.
Yi-Ting
YT
Wang
College of Pharmacy, Shihezi University, Shihezi 832002, China. liguoyulisa@163.com.
Guo-Yu
GY
Li
College of Pharmacy, Shihezi University, Shihezi 832002, China. why_pha@shzu.edu.cn.
Hang-Yu
HY
Wang
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. profwjh@126.com.|College of Pharmacy, Shihezi University, Shihezi 832002, China. profwjh@126.com.
Jin-Hui
JH
Wang
D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D015415:Biomarkers; D001761:Bleomycin / Q000009:adverse effects*; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D010450:Endopeptidases; D018093:Gelatinases / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D029771:Rhodiola / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
D000199:Actins; D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D001761:Bleomycin; D010450:Endopeptidases; D018093:Gelatinases; D005978:Glutathione; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins; D010936:Plant Extracts; D020011:Protective Agents; D012697:Serine Endopeptidases; D013482:Superoxide Dismutase; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D000099167:Fibroblast Activation Protein Alpha
MMP-9; Rhodiola rosea L.; TGF-β1; bleomycin; pulmonary fibrosis