Chemo-proteomics reveals dihydrocaffeic acid exhibits anti-inflammation effects via Transaldolase 1 mediated PERK-NF-κB pathway

Acute pneumonia is a kind of widespread inflammatory pathological process. Dihydrocaffeic acid (DA), metabolite of chlorogenic acid, possesses potent pharmacologic activity for the therapy of a wide range of disorders and various biological properties, such as anti-inflammation. Nevertheless, the specific protein targets and potential molecular mechanisms of DA in acute pneumonia are still poorly understood. To investigate the anti-inflammation effects of DA and its target and its specific mechanisms. Here, we conducted lipopolysaccharides (LPS)-induced acute pneumonia model mice. Besides, the activity-based protein profiling (ABPP) was performed to explore the potential targets of DA. Furthermore, cellular thermal shift assay (CETSA) and pulldown-western blot assays were used to validate the conclusion. In this study, we indicated that DA alleviated acute pneumonia in mice and displayed excellent anti-inflammatory efficacy in vivo and in vitro. Besides, we discovered DA binds directly to transaldolase 1(TALDO1) and influenced its enzymatic activity, and identified the specific cysteine sites Cys250. Also we demonstrated that DA reveals anti-inflammation effect through TALDO1 mediated PERK-IκBα-NF-κB pathway in RAW 264.7 cells. This study provide support for the potential advancement of DA for use as a therapeutic agent for the treatment of acute pneumonia and inflammation-associated diseases.