ABSTRACT
In this study, we evaluated the in vivo effect of arctigenin (ATG) on bleomycin-induced pulmonary fibrosis in mice and assessed the role of antioxidant activity. Hematoxylin and eosin (H&E) staining, the results of Masson's trichrome, and Sirius red staining showed that bleomycin induced obvious pathological changes and collagen deposition in the lung tissue of mice, which were effectively inhibited by ATG. Specifically, based on immunohistochemistry and western blot results, ATG inhibited the expression of fibrosis markers, such as collagen, fibronectin, and α-SMA. Moreover, ATG regulated reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the lung tissue of pulmonary fibrosis mice and reduced the pressure of oxidative stress. ATG also regulated the TGF-ß-induced expression of p-Akt, confirming that ATG can inhibit fibrosis through antioxidant activity modulation.
Subject(s)
Bleomycin , Pulmonary Fibrosis , Animals , Antioxidants/adverse effects , Bleomycin/toxicity , Collagen/metabolism , Fibrosis , Furans , Glutathione/metabolism , Lignans , Lung/pathology , Mice , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolismABSTRACT
This study investigated the inhibitory effects of sanguinarine (SA) on PKC-CPI-17 pathway in rat intestinal smooth muscle cells (ISMC). Previous studies indicate that the inhibitory effects of SA on ISMC contraction are possibly mediated by the Ca(2+) influx. ISMC was treated with 1 µM SA for 24h remarkably inhibited the mRNA expression of m2 and m3 receptors. ISMC treated with 1 or 3 µM SA for 30 min significantly decreased the mRNA expression of PKC-δ, PKC-ε, PKC-η, and CPI-17. 1 µM SA could markedly inhibit carbachol (CCh)-mediated increase PKC-δ, PKC-η, and CPI-17 mRNA but had no effect in PKC-ε.Treatment of ISMC with SA (1 µM, 30 min) caused a decrease in protein expression of PKC-δ. However, the expression of CPI-17 was significantly inhibited in a time-dependent manner. These results demonstrate that the inhibitory effect of SA is coupled with alteration of PKC-mediated signal transduction and intracellular Ca(2+) concentration.
