Attenuation of the Severity of Acute Respiratory Distress Syndrome by Pomiferin through Blocking Inflammation and Oxidative Stress in an AKT/Foxo1 Pathway-Dependent Manner.

Abstract

Acute respiratory distress syndrome (ARDS) gives rise to uncontrolled inflammatory response and oxidative stress, causing very high mortality globally. Pomiferin is a kind of prenylated isoflavonoid extracted from Maclura pomifera, owning anti-inflammatory and antioxidant properties. However, the functions and possible mechanisms of pomiferin in lipopolysaccharide- (LPS-) induced ARDS remain unknown. C57BL/6 mice were injected with LPS (5 mg/kg) intratracheally to induce an in vivo ARDS model while RAW264.7 macrophages were stimulated with LPS (100 ng/ml) to induce an in vitro model. Our data demonstrated that pomiferin (20 mg/kg) significantly improved pulmonary function and lung pathological injury in mice with ARDS, apart from increasing survival rate. Meanwhile, pomiferin treatment also inhibited LPS-induced inflammation as well as oxidative stress in lung tissues. LPS stimulation significantly activated AKT/Foxo1 signal pathway in lung tissues, which could be reversed after pomiferin treatment. In vitro experiments further showed that 10, 20, and 50 μM of pomiferin could enhance cell viability of RAW264.7 macrophages stimulated with LPS. What is more, 3-deoxysappanchalcone (3-DE), one AKT agonist, was used to active AKT in RAW264.7 macrophages. The results further showed that 3-DE could abolish pomiferin-elicited protection in LPS-treated RAW264.7 macrophages, evidenced by activated inflammation and oxidative stress. Taken together, our study showed that pomiferin could exert an ARDS-protective effect by blocking the AKT/Foxo1 signal pathway to inhibit LPS-induced inflammatory response and oxidative injury, which may serve as a potential candidate for the treatment of ARDS in the future.