hydroxysafflor-yellow-a and Pulmonary-Fibrosis

To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats.. Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg•kg. On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO. HSYA could alleviate acute lung inflflammation and chronic pulmonary fibrosis induced by BLM in rats.

Topics: Actins; Animals; Bleomycin; Chalcone; Collagen Type I; Interleukin-1beta; Interleukin-6; Lung; Lung Injury; Oxygen; Pneumonia; Pulmonary Fibrosis; Quinones; Rats, Wistar; RNA, Messenger; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Hydroxysafflor yellow A (HSYA) is an active component of Carthamus tinctorius L., and we want to investigate whether HSYA attenuates pulmonary fibrosis induced by bleomycin (BLM) in mice. The mice received a BLM via oropharyngeal aspiration, and HSYA was intraperitoneally injected. Arterial blood gas analysis was performed. Morphological changes and hydroxyproline content were measured. mRNA expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor, α-smooth muscle actin (α-SMA), and collagen I was measured by real-time polymerase chain reaction. α-SMA-positive cells in lung tissues were detected by immunohistochemical staining. A549 cell was cultured, and morphological changes were observed after TGF-β1 and HSYA treatment. mRNA expression was detected by real-time polymerase chain reaction. Phosphorylation of Smad3 was evaluated by western blotting. HSYA decreased the lung consolidation area and collagen deposition in mice with pulmonary fibrosis. The blood gas changes due to BLM were attenuated by HSYA. HSYA also alleviated the BLM-induced increase of TGF-β1, connective tissue growth factor, α-SMA, and collagen I mRNA levels. HSYA treatment inhibited the increase of α-SMA expression, Smad3 phosphorylation, the morphological changes in lung tissue. HSYA inhibits Smad3 phosphorylation and elevated expression of collagen I mRNA in epithelial-mesenchymal transition induced by TGF-β1.

Topics: Actins; Animals; Bleomycin; Chalcone; Collagen Type I; Connective Tissue Growth Factor; Epithelial-Mesenchymal Transition; Hydroxyproline; Lung; Male; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Pyridines; Quinones; Real-Time Polymerase Chain Reaction; RNA, Messenger; Smad3 Protein; Transforming Growth Factor beta1

Hydroxysafflor yellow A (HSYA) is one of the chemical component isolated from Chinese medicine Carthamus tinctorius L. Our preliminary study confirmed that HSYA attenuated bleomycin-induced pulmonary fibrosis in mice. In this study, we evaluated the effect of HSYA on TGF-β1-induced activation of human fetal lung fibroblasts (MRC-5) and explored the underlying mechanisms of its activity.. MRC-5 cells activated by TGF-β1 were incubated with HSYA and/or the TGF-β type I receptor inhibitor, SB431542. TGF-β1-induced cell proliferation, α-smooth muscle actin, collagen I alpha 1 and fibronectin expression, Smad, mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase/Akt signalling pathway activation were observed.. Hydroxysafflor yellow A significantly inhibited TGF-β1-induced cell proliferation and the expression, both mRNA and protein, of α-smooth muscle actin, collagen I alpha 1 and fibronectin. HSYA also suppressed TGF-β1 activation of Smad signal transduction via inhibition of Smad2 and Smad3 phosphorylation, their nuclear translocation and the binding activity of Smad3 to type I collagen promoter in MRC-5 cells. In addition, HSYA inhibited TGF-β1-induced phosphorylation of extracellular signal-regulated kinase (ERK). The inhibitory effects of HSYA were similar to SB431542.. These findings suggest that HSYA inhibits TGF-β1-induced activation of MRC-5 cells associated with TGF-β1/Smad and ERK/MAPK signalling pathways.

Topics: Actins; Benzamides; Cell Proliferation; Cells, Cultured; Chalcone; Collagen Type I; Dioxoles; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Fibronectins; Humans; Lung; Protein Serine-Threonine Kinases; Pulmonary Fibrosis; Quinones; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1