α-Phellandrene, a cyclic monoterpene, attenuates inflammatory response through neutrophil migration inhibition and mast cell degranulation

Aims: We aimed to investigate the modulating effect of alpha-phellandrene on neutrophil migration and mast cell degranulation processes. Main methods: Male Wistar rats or Swiss mice were treated p.o. with vehicle (3% Tween 80, p.o.), alpha-phellandrene (50, 100, or 200mg/kg, p.o.), or dexamethasone (0.5 mg/kg, p.o.) 1 h before carrageenan injection. Then, the neutrophil migration in 6-day-old air pouches or peritoneal cavities. The leukocyte rolling and adhesion were measured in real time and assessed by intravital microscopy. ELISA was used to detect TNF-alpha and IL-6 in peritoneal lavage. Compound 48/80-induced mast cell degranulation was assessed in mesenteric rat tissues. Key findings: In all the tested doses, alpha-phellandrene prevented carrageenan-induced neutrophil accumulation (P < 0.05). As detected by intravital microscopy, alpha-phellandrene also inhibited leukocyte rolling and adhesion, as well as significantly inhibited the production of the pro-inflammatory cytokines TNF-alpha and IL-6. Moreover, the degranulation of compound 48/80-induced mast cells was also inhibited by alpha-phellandrene (P < 0.001). Significance: These results suggest that alpha-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization. (C) 2016 Elsevier Inc. All rights reserved.