Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs

• The mucoactive effect of naringin in pathological in vivo models was investigated.
• Naringin exhibits mucoactive effects through multiple targets.
• Naringin reduces of goblet cells hyperplasia and mucus hypersecretion.
• Naringin promotes sputum excretion.

Our previous study has demonstrated that naringin attenuates EGF-induced MUC5AC hypersecretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/IκB/NF-κB signaling pathways. However, the volume of airway mucus is determined by two factors including the number of mucous cells and capacity of mucus secretion. The aim of the present study is to explore the mucoactive effects of naringin in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and beagle dogs. The results demonstrated that naringin of 12.4 mg/kg treatment significantly decreased LPS-induced enhancement of sputum volume and pulmonary inflammation, remarkably increased the subglottic sputum volume and solids content in sputum of lower trachea, while partially, but not fully, significantly increased the elasticity and viscosity of sputum in lower trachea of beagle dogs. Moreover, the MUC5AC content in BALF and goblet-cells in large airways of LPS-induced ALI mice were significantly attenuated by dexamethasone (5 mg/kg), ambroxol (25 mg/kg), and naringin (15, 60 mg/kg). However, the goblet-cells hyperplasia in small airways induced by LPS was only significantly inhibited by dexamethasone and naringin (60 mg/kg). In conclusion, naringin exhibits mucoactive effects through multiple targets which including reduction of goblet cells hyperplasia and mucus hypersecretion, as well as promotion of sputum excretion.