Potentilla paradoxa Nutt. Ethanol Extract Exhibits Anti-Inflammatory Effects by Suppression of the Src/NF-κB Signaling Pathway

Abstract

Inflammation is an immune response that protects against harmful stimuli. However, severe inflammation can cause many diseases, such as diabetes, cancer, and arthritis. In this study, we examined the anti-inflammatory efficacy and mechanism of Potentilla paradoxa Nutt. ethanol extract (Pp-EE) as a new strategy for controlling the inflammatory response. Cellular activities and the molecular target of Pp-EE were identified in RAW264.7 cells and HEK293T cells. The effect of Pp-EE was analyzed using the Griess assay, the luciferase assay, reverse transcription-polymerase chain reaction, and Western blotting. To evaluate the in vivo effects, an HCl/EtOH-induced gastritis mouse model was used. NO production and pro-inflammatory gene (iNOS, COX-2, and TNF-α) mRNA levels were decreased by Pp-EE in a concentration-dependent manner without showing cytotoxicity. The activation of the transcription factor, particularly NF-κB, was effectively suppressed by Pp-EE. It was also found that Pp-EE directly inhibits the activation of Src in lipopolysaccharide (LPS)-treated RAW264.7 cells and in Src-overexpressed HEK293 cells by Western blotting analysis and cellular thermal shift assay. Experiments in the gastritis mouse model indicated that Pp-EE suppresses HCl/EtOH-induced gastric lesions, the expression levels of COX-2, IL-6, and TNF-α, and the phosphorylation of p65, p50, and Src. Taken together, these results suggest that Pp-EE can be applied as an anti-inflammatory remedy with a Src/NF-κB inhibitory property.