title: Prevention of pulmonary fibrosis with salvianolic acid a by inducing fibroblast cell cycle arrest and promoting apoptosis.
abstract: BACKGROUND
  Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine (TCM), often in combination with other herbs, to treat a diversity of ailments. More recent studies have focused on its possible roles in the treatment of respiratory diseases (pneumonia and pulmonary fibrosis) and found that it has pharmacological activity that protects pulmonary morphology and function. However, the mechanism underlying this activity has not yet been clarified.
  
  
  METHODS
  The purpose of this study was to investigate the anti-pulmonary fibrosis effects exerted by salvianolic acid A (SAA), the ingredient responsible for the pharmacological activity of Danshen, and the underlying mechanisms. Bleomycin (BLM)-induced rat pulmonary fibrosis was used to evaluate the antifibrotic role of SAA, and fibroblast cells were used to study the mechanism involved.
  
  
  RESULTS
  BLM-treated rats exhibited increased alveolar wall thickness and collagen deposition in lung tissues, but these pathologies were greatly attenuated by daily administration of SAA. We also found that SAA significantly inhibited the proliferation, adhesion and migration of fibroblasts in vitro. This was partly due to a strong induction of cell cycle arrest and apoptosis upon SAA treatment. Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclin D1, cyclin E1, and cyclin B1, and increased expression of p53 and p21 in SAA-treated cells. In addition, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while cleaved caspase-3 protein increased upon SAA treatment.
  
  
  CONCLUSIONS
  These results suggest that the alleviation of rat pulmonary fibrosis by SAA is due to the inhibition of fibroblast proliferation and induction of apoptosis, which occurs mainly through p53-dependent growth arrest and apoptosis. We suggest that SAA should be considered as a potential novel therapeutic agent for the treatment of fibrotic lung diseases.
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Center Laboratory, Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Fu
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Qiyang
authors.initials: Q
authors.lastname: Shou
authors.affiliation: Program in Molecular Cell Biology, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Program in Molecular Cell Biology, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: cmli991@aliyun.com.
authors.forename: Minli
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D017208:Rats, Wistar
chemical_list: D002109:Caffeic Acids; D007773:Lactates; D001761:Bleomycin; C066201:salvianolic acid A
keywords: Apoptosis; Cell cycle; Phenotypic modulation; Pulmonary fibrosis; Salvianolic acid A