Eugenol Exerted Significant Anti-Oxidant and Anti-Inflammatory Effects on Experimental Colitis via Directly Acting on PPAR-[Formula: see text].

Abstract

In a previous study, Eugenol (EU) has been demonstrated to alleviate DSS-induced experimental colitis, due to its anti-inflammatory, anti-oxidant, and immune regulatory efficacy, but its underlying molecular mechanism remains unknown. In this study, EU applications were combined with peroxisome proliferator-activated receptor-[Formula: see text] (PPAR-[Formula: see text]) agonist (rosiglitazone) and inhibitor (GW9662) in order to clarify the role of PPAR-[Formula: see text] in EU against UC by testing NF-κB and Nrf2 signaling pathway activation and the salient features of colitis. The binding activity and adjusting effect of EU on inflammation and oxidative stress were further investigated in vitro. Similar to rosiglitazone, the results illustrated that EU remarkably reversed DSS-induced weight loss, reversed colonic shrinkage and integrity damage, and inhibited the DAI scores increase, excessive inflammatory response, and oxidative stress. However, the combination with GW9662 noticeably restrained the protective effect on mice. Additionally, molecular docking and a surface plasmon resonance assay evidenced the direct binding activity of EU with PPAR-[Formula: see text]. EU's anti-oxidant and anti-inflammation bioactivities were evidenced again in vitro. Overall, the above results further demonstrated the molecular mechanism of EU's defensive effect, which is directly dependent on PPAR-[Formula: see text] activation, on experimental colitis. Therefore, this study may facilitate a better understanding of EU's protective action against UC.