Background: Wedelolactone, main active constituent of Wedelia calendulace and Eclipta alba plants which has been traditionally used to treat various chronic inflammatory conditions. However, its mechanism of action of anti-inflammatory effect on ulcerative colitis is yet to be established.

Objective: In the present study, the effect of the wedelolactone on the myeloperoxidase activities and in the production of proinflammatory cytokines involved in the pathogenesis of chronic inflammation was assessed.

Methods: Wistar rats were randomly divided into four groups containing six animals per group. Group I (Vehicle control): tap water and vehicle; Group II (DSS control): tap water containing 5% (w/v) of DSS over 7 days, and vehicle; Group III (treatment group): Wedelolactone 50 mg/kg/day, and tap water containing 5% DSS over 7 days, Group IV (treatment group): Wedelolactone 100 mg/kg/day and tap water containing 5% DSS over 7 days over the experiment.

Results: Study revealed that wedelolactone treatment dramatically decrease the release of IL-1a, IL-1b, IL-2, TNF, INFγ, STAT3 and CCL-5 in colons treated with DSS. In summary, these results suggest that the inhibition of IL-6/STAT3 signaling is a potential mechanism by which wedelolactone is used in the treatment of ulcerative colitis.

Conclusions: Oral administration of Wedelolactone (100 mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase activities. In summary, Wedelolactone showed anti-inflammatory effect by down regulation of the IL-6/STAT3 inflammatory signaling pathway. These findings provide new insights into the pharmacological actions of wedelolactone as a potential therapeutic agent for colitis.