Examination of the protective effect of 6-shogaol against LPS-induced acute lung injury in mice via NF-kB attenuation

Abstract

Acute lung injury (ALI), the causative factor for acute respiratory distress syndrome, results in significant morbidity and mortality. Due to a lack of effective therapeutic options for ALI, the development of novel therapies is urgently needed. NF-?B, an inflammatory mediator necessary for the evolution of ALI, could serve as an important target for novel agents to prevent disease progression. The present study was designed to evaluate the protective effect of 6-shogaol against lipopolysaccharide (LPS)-induced ALI in mice, and its mechanism of action. Our results suggest that 6-shogaol significantly attenuates elevated levels of various proinflammatory cytokines, such as tumor necrosis factor alpha (TNF?), IL-1? and IL-6. Moreover, the influx of neutrophils, increased protein concentration and edema were also suppressed in mice pretreated with 6-shogaol. These observations were also confirmed by histopathological examination of lung tissues, which suggests that 6-shogaol significantly improves the pathological condition to normal in a dose-dependent manner. A docking study of 6-shogaol was also performed, with the NF-?B p50 homodimer bound to a ?B site, to determine its possible inhibitory effects. Our results show that 6-shogaol was efficiently accommodated in the deep cleft of the active site, lined with residues Tyr57, Val58 and Cys59, Tyr143, Lys145 and Lys146 of Chain B of p50 NF-?B.