Allicin-induced AMPK signaling attenuated canonical TGFβ1/SMAD3 pathway-mediated lung fibrosis

Abstract

Abstract Background: 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 underlying mechanisms of action. Methods: The effects of allicin on fibronectin-mediated lung fibroblast migration and the contraction of three-dimensional type I collagen gels were assessed. Furthermore, the anti-fibrotic effect of allicin was evaluated in a mouse model of bleomycin (BLM)-induced lung fibrosis. Results: Allicin suppressed TGFβ1-stimulated gel contraction and migration as well as α-SMA and fibronectin expression (P < 0.05). Allicin up-regulated AMP-activated protein kinase (AMPK) phosphorylation while suppressing SMAD3 phosphorylation. AMPK inhibitor further stimulated TGFβ1-induced gel contraction and migration (P < 0.05). Allicin suppressed BLM-induced lung fibrosis and lung injury in a mouse model, with substantial reductions in inflammatory cell infiltration in the bronchoalveolar lavage fluid (P < 0.05). Conclusion: Allicin may be a candidate therapeutic agent for lung fibrosis. Furthermore, its effects were mediated by AMPK pathways; these findings may guide further research aimed at the development of fibrosis treatments.