Lipoxins and novel 15‐epi‐lipoxin analogs display potent anti‐inflammatory actions after oral administration

Lipoxins (LX) and aspirin‐triggered 15‐epi‐lipoxins (ATL) exert potent anti‐inflammatory actions. In the present study, we determined the anti‐inflammatory efficacy of endogenous LXA4 and LXB4, the stable ATL analog ATLa2, and a series of novel 3‐oxa‐ATL analogs (ZK‐996, ZK‐990, ZK‐994, and ZK‐142) after intravenous, oral, and topical administration in mice. LXA4, LXB4, ATLa2, and ZK‐994 were orally active, exhibiting potent systemic inhibition of zymosan A‐induced peritonitis at very low doses (50 ng kg−1–50 μg kg−1). Intravenous ZK‐994 and ZK‐142 (500 μg kg−1) potently attenuated hind limb ischemia/reperfusion‐induced lung injury, with 32±12 and 53±5% inhibition (P