LAUSR

ABSTRACT Endothelial cell injury and subsequent inflammation play pivotal roles in the pathogenesis of pulmonary fibrosis, a progressive and fatal disorder. We found previously that salvianolic acid B (SAB) attenuated experimental pulmonary fibrosis. Pulmonary fibrosis is driven by inflammation, but the anti‐inflammatory role and mechanism of SAB on the treatment of pulmonary fibrosis is still unknown. Here, our in vivo studies showed that SAB had a strong anti‐inflammatory effect on bleomycin‐instilled mice by inhibiting inflammatory cell infiltration and inflammatory cytokine production. Moreover, SAB protected endothelial cells against oxidative stress injury and inhibited endothelial cell apoptosis in bleomycin‐treated mice. The in vitro studies also showed that SAB decreased the H2O2‐induced overproduction of reactive oxygen species to protect EA.hy926 endothelial cells from oxidative damage, and further inhibited H2O2‐induced permeability and overexpression of pro‐inflammatory molecules. The next studies revealed that SAB inhibited the H2O2‐induced cell apoptosis and attenuated the decrease of tight junction‐related gene expression, resulting in a decrease of the endothelial permeability in injured endothelial cells. Furthermore, Western blot analysis suggested that SAB decreased endothelial cell permeability and expression of pro‐inflammatory cytokines by inhibiting MAPK and NF‐&kgr;B signaling pathways. Taken together, these data indicate that SAB exerted anti‐inflammatory roles in pulmonary fibrosis by protection of the endothelial cells against oxidative stress injury, mediated by inhibition of endothelial permeability and expression of pro‐inflammatory cytokine via the MAPK and NF‐&kgr;B signaling pathways. Graphical abstract Figure. No caption available.