Allicin induced AMPK signaling attenuated Smad3 pathway mediated lung fibrosis.

Allicin, a natural compound derived from garlic, protects against oxidative stress-mediated tissue inflammation and vascular remodeling. Although these are key processes in lung fibrosis, the effects of allicin on this disease have never been evaluated. In this study, we aimed to evaluate the effects of allicin on lung fibroblast-mediated lung fibrosis and its mechanisms. We assessed the effects of allicin on fibronectin-mediated lung fibroblast migration and the contraction of three-dimensional type I collagen gels, and evaluated its anti-fibrotic effects in mice models of bleomycin (BLM)-induced lung fibrosis. The results showed that allicin suppressed transforming growth factor beta 1 (TGFβ1)-stimulated gel contraction and migration, as well as α-smooth muscle actin (α-SMA) and fibronectin. Additionally, allicin upregulated AMP-activated protein kinase (AMPK) phosphorylation, while suppressing Smad3 phosphorylation. An AMPK inhibitor further stimulated TGFβ1-induced gel contraction and migration. Furthermore, allicin suppressed BLM-induced lung fibrosis with suppressed Smad3 phosphorylation and BLM-induced lung injury with suppressed inflammatory cell infiltration in the mouse models. These results suggest that allicin may be a candidate therapeutic agent for suppressing the fibrotic phase mediated by pulmonary fibroblasts through upregulated AMPK resulting in suppressed Smad3 pathway after reducing the acute inflammatory phase.