Icariin alleviates transforming growth factor-β1-induced epithelial-mesenchymal transition by targeting Smad and MAPK signaling pathways.

The pathogenesis of airway remodeling and airway inflammation is related to epithelial-mesenchymal transition (EMT), which is correlated with TGF-β1 levels. Icariin is one of the major compounds in Epimedium brevicornum Maxim, and plays emerging roles in relieving cough and asthma, enhancing immunity, and anti-allergy. In the present study, we investigated the mechanism through which Icariin inhibits inflammatory and airway remodeling in vitro and in vivo. In vitro, 16HBE cells were stimulated with 10 ng/ml TGF-β1 for 24 hours to induce EMT model. Whereas pretreatment with Icariin could alleviate EMT both in concentration- and time-dependent manner, as was evidenced by the improved cell morphology, reduced migration, down-regulation of mesenchymal markers (N-cadherin, α-SMA), and up-regulation of epithelial marker (E-cadherin). In vivo, female BALB/c mice were exposed to 25 mg/ml house dust mites (HDM) extract for 5 days and followed by 2 days rest for 5 weeks to induce chronic asthma model. Of note, administration of Icariin could attenuate airway responsiveness, inflammation, and fibrosis, with improved scores based on the staining of H&E, PAS, and Sirius Red. In addition, Icariin reduced the levels of TGF-β1 in bronchoalveolar lavage fluid (BLAF), serum, and lung tissue, and regulated the expression of EMT markers. At the molecular level, Icariin inhibits the phosphorylation of Smad-2, Smad-3, Erk, JNK, and p38 both in vitro and in vivo. Taken together, Icariin inhibits airway remodeling by attenuating TGF-β1-induced EMT through targeting Smad and MAPK signaling.