Sodium Formononetin-3'-sulfonate attenuated acute lung injury by Fas/PDK1/STAT Signaling

Formononetin is an isoflavone compound, and sodium formonetin-3'-sulfonate (ND308) is the salt form of formononetin, which is convenient for injection administration. However, the therapeutic effects elicited by ND308 toward acute lung injury (ALI) remain unclear.

In this study, we performed an in vivo investigation in rats on ND308's effect on ALI resulting from LPS-induced two-hit rat model. Then, we focused on the mechanisms by which ND308' inhibits experimentally induced experimental ALI in vitro by determining its effect on human pulmonary microvascular endothelial cells (HMs) stimulated by LPS.

Continuous ND308 administration at 20 mg/kg for 3 days elicited protective effects in the LPS-induced rat experimental ALI model, as reflected in changes in Hounsfield units as an indicator of overall pulmonary function, lung microscopic pathology scores and in the lung coefficient as indicators of gross pulmonary pathology. Protein expression levels of FAS, p-PDK1, p-STAT3, and PDK1 distribution in nuclei reduced significantly, whereas, tight junction (TJ) protein claudin 18.1 increased significantly. In in vitro studies, LPS-induced HMs showed similar results; lower FAS, p-PDK1, p-STAT3, and PDK1 distribution in nuclei and higher claudin 18.1 expression.

Overall, ND308 appeared to alleviate ALI by strengthening claudin 18.1 expression via FAS/PDK1/STAT3 inhibition.