Geniposidic acid protects lipopolysaccharide-induced acute lung injury via the TLR4/MyD88 signaling pathway in vitro and in vivo

Abstract

Background Acute lung injury (ALI) is a common respiratory disease and is a serious threat to human health due to the lack of effective treatment. Geniposidic acid (GPA) is an iridoid glucoside extracted from Gardeniae jasminoides Ellis and can treat inflammation-related diseases. This study aimed to investigate the regulatory functions of GPA on lipopolysaccharide (LPS)-induced ALI and its potential mechanism, providing effective strategies for the clinical treatment of ALI. Methods ALI models were constructed by LPS in Sprague-Dawley rats and pulmonary epithelial cells. The function of GPA was investigated by hematoxylin–eosin staining, lung function assessment, Western blot, Masson staining, and Sirius Red staining, quantitative real-time PCR, enzyme-linked immunosorbent assay, cell counting kit-8 assay, apoptosis analysis, and immunofluorescence assays. Results Functionally, GPA increased survival, relieved pulmonary epithelial function in response to LPS, repressed pulmonary fibrosis and inflammation caused by ALI in vivo; GPA also repressed pulmonary epithelial cell injury and inflammation induced by LPS in vitro. Mechanistically, GPA decreased the protein levels of TLR4 and MyD88 and accelerated the nuclear export of p65, suggesting that GPA repressed the activation of p65. Conclusion GPA protected LPS-induced ALI through the TLR4/MyD88 signaling pathway.