Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury.

ABSTRACT: Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37?±?1.59??g/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86?±?0.06??M). In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.

SUBMITTER: Chen YL 

PROVIDER: S-EPMC5041076 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature