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

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.

Rhodiola species: A comprehensive review of traditional use, phytochemistry, pharmacology, toxicity, and clinical study

“…The 95% ethanol extract of R. rosea (Extract 76) could alleviate fibrotic lung injury in PF rats dose-dependently (125,250, and 500 mg/kg/d). 182 HYP was reduced by R. rosea, along with increase of GSH and T-SOD. Meanwhile, the bronchoalveolar lavage fluid levels of TNF-α, TGF-β1, and IL-6 were decreased.…”

“…The lung‐protective effect of R. rosea has been investigated on BLM‐induced pulmonary fibrosis (PF) rat model. The 95% ethanol extract of R. rosea (Extract 76 ) could alleviate fibrotic lung injury in PF rats dose‐dependently (125, 250, and 500 mg/kg/d) . HYP was reduced by R. rosea , along with increase of GSH and T‐SOD.…”

Anti-Fibrotic Potential of Nicorandil in the Treatment of Bleomycin Induced Pulmonary Fibrosis

“…In addition, several studies have demonstrated that bleomycin administration in rats decreased the anti-oxidative capacity and increased oxidative stress in the lung tissue, which aggravated pulmonary fibrosis. 13,14,15 It has been established that in bleomycin induced pulmonary fibrosis the levels of the biochemical, oxidant and antioxidant parameters changed significantly than those of the normal levels. This is evident by increased levels Lactate Dehydrogenase (LDH) which is a marker of biochemical index.…”

“…Previous studies demonstrated that anti-oxidant agents ameliorated the accumulation of leukocytes in bronchial lavage fluid and lung tissue which agrees with our findings. [12][13][14][15][16][17][18][19] The pathophysiology of Bleomycin-induced lung injury typically consisted of two overlapping stages; an early inflammatory phase characterized by leukocyte infiltration and injury to alveolar epithelial cells, and a subsequent fibro-proliferative phase with matrix remodeling and fibrosis. 20 Haematoxylin & Eosin (H&E) staining results in BLM control group showed that acute inflammations were prominent with moderate or severe hemorrhage, widened alveolar septa, and infiltration of numerous inflammatory cells predominated by macrophages, neutral granulocytes, and lymphocytes.…”

Efecto antifibrotico de Lepidium peruvianum en un modelo de fibrosis pulmonar inducida con nanosi­lice en ratas

“…Por otro lado, los hallazgos histopatológicos son comparables con otros estudios que evalúan efectos potenciales de plantas medicinales. Por ejemplo, Zhang et al al evaluar el efecto antifibrótico del extracto etanólico de Rhodiola rosea L. encontraron una disminución discreta de los cambios histopatológicos mostrados y de las fibras de colágeno alrededor de los vasos pulmonares en comparación a lo mostrado por el control (inducido con bleomicina) [33] ; mientras que M. Iraz et al, encontraron que la administración de una solución acuosa de Ginkgo biloba, podía prevenir el incremento del índice de Ashcroft en los ratones a los que se les induce fibrosis con bleomicina [34] .…”