tanshinone-ii-a-sodium-sulfonate and Pulmonary-Fibrosis

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by interstitial inflammation and fibrosis. Salvianolic acid B (SAB) and sodium tanshinone IIA sulfonate (STS) are representative components in Salvia miltiorrhiza, which have been reported using in the treatment of PF. The aim of the study was to explain the role of inflammation in the process of PF and to investigate the effect of SAB and STS on inflammation and fibrosis in vitro. The results clearly indicated that lipopolysaccharide (LPS)-stimulated inflammatory response could induce fibroblast proliferation and fibroblast to myofibroblast transformation (FMT). Both SAB and STS significantly inhibited LPS-induced inflammation in vitro, including down-regulated the protein expression levels of IL-1β and TNF-α and the mRNA expression levels of IL1B and TNFA. Furthermore, both SAB and STS inhibited TGF-β1-induced the proliferation in MRC-5 cells and the overexpression of α-SMA and COL1α1, both the protein and mRNA levels. In conclusion, these results indicate that the inflammatory response is necessary for the development of PF, and the therapeutic effect of SAB and STS on PF may be related to anti-inflammatory and anti-fibrotic effects.

Topics: Actins; Anti-Inflammatory Agents; Benzofurans; Cell Proliferation; Coculture Techniques; Collagen Type I; Collagen Type I, alpha 1 Chain; Cytokines; Fibroblasts; Humans; Inflammation Mediators; Lung; Macrophages; Phenanthrenes; Pneumonia; Pulmonary Fibrosis; THP-1 Cells

Silicosis is characterized by pulmonary fibrosis due to long-term inhalation of silica particles. Although the cause of this serious disease is known, its pathogenesis remains unclear and there are currently no specific treatments. Recent studies have shown that the anti-oxidant transcription factor Nrf2 is expressed at reduced levels in fibrotic foci, which may be related to disease progression. However, the molecular mechanisms by which this might occur have yet to be elucidated. Sodium tanshinone IIA sulfonate (STS), an extract of Salvia miltiorrhiza, is used in traditional Chinese medicine in the treatment of coronary heart disease. STS has been shown to play a strong anti-oxidative role in various organs. Here, we employed a rat model to explore the effects of STS on oxidative stress and the progression of fibrosis in silicosis. STS significantly reduced collagen deposition in the lungs, thereby antagonising silicosis. Immunohistochemical and immunofluorescence staining showed that Nrf2 was differentially expressed in lung cells during silica induced fibrosis, and chromatin immunoprecipitation-sequencing experiments demonstrated that Nrf2 promoted the expression of the antioxidant proteins thioredoxin and thioredoxin reductase. Our results suggest that the anti-fibrotic effects of STS may be related to upregulation of Nrf2 nuclear expression, especially in fibrotic lesions, and the promotion of thioredoxin and thioredoxin reductase expression. Our findings may open up new avenues for the development of STS as a treatment for silicosis.

Topics: A549 Cells; Animals; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Inhalation Exposure; Male; Mice; NF-E2-Related Factor 2; Particle Size; Phenanthrenes; Pulmonary Fibrosis; Rats; Rats, Wistar; RAW 264.7 Cells; Silicon Dioxide; Silicosis; Surface Properties; Thioredoxins

Study was designed to explore the effect of sodium tanshionone IIA sulfonate on bleomycin-induced pulmonary fibrosis in rat. The amount of lipid peroxides (LPO), hydroxyproline in rat lung tissue homogenate was determined at 3, 7, 14, 28 day after administration respectively. The results suggest that the amount of LPO, hydroxyproline of rat lung homogenate were significantly decreased in sodium tanshionone IIA sulfonate group. In addition, histological changes and width of alveolar septa and percentage area of pulmonary fibrosis scars was measured. The results show that sodium tanshionone IIA sulfonate could ameliorate bleomycin induced pulmonary fibrosis in rat. The mechanism that sodium tanshionone IIA sulfonate could prevent and treat bleomycin-induced pulmonary fibrosis in rat was discussed.

Topics: Animals; Bleomycin; Drugs, Chinese Herbal; Female; Hydroxyproline; Lipid Peroxides; Lung; Male; Phenanthrenes; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley