Fucoxanthin inhibits profibrotic protein expression in vitro and attenuates bleomycin-induced lung fibrosis in vivo.

Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated. We performed an enzyme-linked immunosorbent assay (ELISA), and a western blot analysis to elucidate the mechanisms underlying the antifibrotic effects of Fx in TGF-β1-stimulated cells. The contractile activity of HPFs was measured using a collagen gel contraction assay. We also investigated the effects of Fx on inflammation and fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse model. We observed that Fx inhibited the TGF-β1-induced expression of α-SMA, type 1 collagen, fibronectin, and IL-6 in HPFs. Similarly, markedly inhibition of TGF-β1-induced phosphorylation of p-38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and Smad2/Smad3 (Smad2/3) was observed after Fx treatment. Collagen contraction also significantly decreased on fucoxanthin treatment. Intraperitoneal injection of Fx (10mg/kg) in mice inhibited BLM-induced lung fibrosis and type I collagen protein expression. Overall, our findings suggest that Fx may be effective in the treatment of pulmonary fibrosis owing to its potent antifibrotic activity.