Psoralidin, a dual inhibitor of COX‐2 and 5‐LOX, regulates ionizing radiation (IR)‐induced pulmonary inflammation

Abstract

Radiotherapy is the most significant non‐surgical cancer treatment, however it is restricted by two major problems: radioresistance and normal tissue damage. We focused on radiation‐induced normal cell damage, and are concerned with inflammation as a main limiting factor in the radiotherapy. Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia , has been studied for various biological properties. However, little is known regarding its effects on IR‐induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR‐induced inflammation and to examine therapeutic mechanisms of psoralidin. We demonstrated that IR‐induced ROS activated COX‐2 and 5‐LOX pathway in HFL‐1 and MRC‐5 cells. Psoralidin inhibited the IR‐induced COX‐2 expression and PGE 2 production through regulation of PI3K/Akt and NF‐κB signaling. Also, psoralidin blocked IR‐induced LTB 4 production through a direct interaction of psoralidin and FLAP. IR‐induced fibroblast migration was notably attenuated by psoralidin. Moreover, psoralidin suppressed IR‐induced expression of pro‐inflammatory cytokines and ICAM‐1 in vivo . Taken together, our findings reveal a regulatory mechanism of IR‐induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin may be useful as a potential radiopreventive agent against radiation‐induced normal tissue injury.