Prevention of pulmonary fibrosis with salvianolic acid a by inducing fibroblast cell cycle arrest and promoting apoptosis.
ETHNOPHARMACOLOGICAL RELEVANCE
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.


MATERIALS AND 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.
['Pan|Yongming|Y|', 'Fu|Huiying|H|', 'Kong|Qing|Q|', 'Xiao|Yin|Y|', 'Shou|Qiyang|Q|', 'Chen|Hongqiang|H|', 'Ke|Yuehai|Y|', 'Chen|Minli|M|']
D000818:Animals D017209:Apoptosis D001761:Bleomycin D002109:Caffeic Acids D002448:Cell Adhesion D059447:Cell Cycle Checkpoints D002460:Cell Line D002465:Cell Movement D005347:Fibroblasts D007773:Lactates D008297:Male D051379:Mice D011658:Pulmonary Fibrosis D017208:Rats, Wistar
Pulmonary fibrosis Salvianolic acid A Cell cycle Apoptosis Phenotypic modulation