4-Hydroxycinnamic acid protects mice from cigarette smoke-induced pulmonary inflammation via MAPK pathways

Abstract

Cigarette smoke (CS) is the main etiological cause of chronic obstructive pulmonary disease, the prevalence of which has continuously increased in recent years. 4-Hydroxycinnamic acid (HA) is a plant phenolic acid that has anti-inflammatory activities. In this study, we explored the therapeutic effects of HA on airway inflammation caused by CS and lipopolysaccharide (LPS) in mice. The animals received 1 h of CS exposure for 7 days and intranasal instillation of LPS on day 4. HA (10 and 20 mg/kg) was administered to animals via oral gavage 1 h before CS exposure. HA treatment significantly decreased the accumulation of inflammatory cells and production of cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, caused by CS and LPS exposure. After histological examination, we observed that HA treatment significantly reduced the infiltration of inflammatory cells into lung tissue caused by CS and LPS exposure. Furthermore, HA-treated groups showed significantly decreased phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor-κB, and activity of cytochrome c oxidase subunit-2 caused by CS and LPS. In conclusion, HA effectively suppresses the airway inflammatory response induced by CS and LPS exposure, and is closely associated with the downregulation of mitogen-activated protein kinases signaling.