Acteoside alleviates asthma by modulating ROS-responsive NF-kB/MAPK signaling pathway

Asthma is a poorly curable disease and more reliable and effective medications are urgently required. Acteoside is a phenypropanoid glycoside widely distributed in diverse herbs and has been demonstrated to possess both anti-inflammatory and antioxidative properties in a range of disorders. While, there was few study of the impact of acteoside on asthma. Therefore, we sought to study the protective effects of acteoside on asthma and inves-tigate the underlying mechanism in vivo and vitro. In ovalbumin (OVA) sensitized mice acteoside significantly inhibited airway hyperresponsiveness (AHR), production of inflammatory cytokines (TNF-a, IL-4, IL-13, IL-33, VEGF and active TGF-81), serum of OVA-specific IgE and the expression of TGF-81 protein in asthmatic mice. In addition, acteoside significantly suppressed goblet cell and airway smooth muscle hyperplasia and collagen deposition. Acteoside might have a better therapeutic against airway remodeling than dexamethasone. More -over, acteoside attenuated OVA-induced oxidative stress paramaters (including ROS, NO and MDA), and decreased the expression of NOX4 and iNOS protein, promoted AMPK activity and increased the expression of antioxidant enzymes (SOD, HO-1, and catalase). Furthermore, we found acteoside notably reduced the levels of proinflammatory proteins (MCP-1, IL-8 and ICAM-1) and intracellular ROS in TNF-a-induced human bronchial epithelial cells. Additionally, acteoside suppressed the activization of NF-xB and MAPK pathway in vivo and vitro. Taken together, our results demonstrated acteoside alleviated asthmatic airway inflammation and remodeling by inhibiting ROS genreation and inactivating NF-xB/MAPK pathways. This provided a novel therapeutic agent for asthma management.