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

Abstract

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 investigate the underlying mechanism in vivo and vitro. In ovalbumin (OVA) sensitized mice acteoside significantly inhibited airway hyperresponsiveness (AHR), production of inflammatory cytokines (TNF-α, IL-4, IL-13, IL-33, VEGF and active TGF-β1), serum of OVA-specific IgE and the expression of TGF-β1 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. Moreover, 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-α-induced human bronchial epithelial cells. Additionally, acteoside suppressed the activization of NF-κB 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-κB/MAPK pathways. This provided a novel therapeutic agent for asthma management.