Inhibitory effect of trans-anethole in acute inflammation: involvement of macrophage-derived mediators

This study investigated in vivo and in vitro the trans-anethole anti-inflammatory activity on vascular and cell events and the involvement of inflammatory mediators. In vivo Wistar male rats (180 - 200 g; n=6/group) received trans-anethole per oral and the anti-inflammatory activity was assessed on the models of paw edema, peritonitis and air pouch. In vitro, peritoneal macrophages were incubated with trans-anethole to evaluate cytotoxicity, cytokines and reactive oxygen species (ROS) stimulated by phorbol myristate acetate (PMA). In vivo trans-anethole (1 mg/kg) inhibited: edema (42%), vascular permeability (58%), migration of total leukocytes (50%) and neutrophils (42%), IL-1β (75%), IL-6 (61%), macrophage inflammatory protein-MIP-3α (64%), NO2 -/NO3 - (35%), malondialdehyde (MDA) and histological alterations induced by carrageenan. Trans-anethole (25 μM) also inhibited polymorphonuclear migration (90%), MIP-3α (83%) and TNF-α (60%) challenged by LPS. In vitro trans-anethole (10 - 50 μM) increased IL-6 per se and reduced inflammatory mediators released by macrophages: TNF-α (up to 80%) and IL-1β (up to 81%) challenged by LPS, and ROS (up to 43%) by PMA, without causing cytotoxicity. In conclusion, trans-anethole has anti-inflammatory effects on vascular and cellular events of acute inflammation via inhibition of cytokines and free radicals produced by macrophages.