Ulcerative colitis (UC) is a long-lasting inflammatory illness of unknown cause that affects the gastrointestinal tract. Despite the anti-inflammatory and antioxidant properties of paeonol, the specific mechanisms by which it treats UC are still not fully understood.

This study aimed to examine the processes by which paeonol acts on ulcerative colitis (UC) using in-vitro and in-vivo experiments employing NCM460 cells, RAW264.7 cells, and a mouse model of colitis caused by dextran sulfate sodium (DSS).

The in vitro studies showed that paeonol inhibits the activation of the NF-κB signaling pathway by increasing the expression of PPARγ. This leads to a decrease in the production of pro-inflammatory cytokines, a reduction in reactive oxygen species levels, and an enhancement of M2 macrophage polarization.

The inclusion of the PPARγ inhibitor GW9662 greatly eliminates these effects. In addition, animals with UC that were treated with paeonol exhibited elevated expression of PPARγ, resulting in decreased inflammation and apoptosis, therefore preserving the integrity of the intestinal epithelial barrier. Findings indicate that paeonol effectively suppresses the NF-κB signaling cascade by activating PPARγ. This leads to a reduction in inflammation and oxidative stress, ultimately alleviating colitis produced by Dss. This work offers a novel perspective on the therapeutic mechanism of paeonol in the treatment of UC.