Evaluation of Anti-Inflammatory Effect of Wedelolactone on Indomethacin Induced Colitis in Rats: Involvement of IL-6/STAT3 Pathway

Abstract

The present study was carried out to study coumestan derivative wedelolactone in Indomethacin-induced enterocolitis in rats. Wistar rats were randomly divided into three groups containing six animals per group. Group I served as normal control. Group II, Group III & Group IV receive 7.5 mg/kg, s.c, indomethacin on two consecutive days. Group III and Group IV have received a wedelolactone dose of 50 mg/kg, and 100 mg/kg per oral, respectively, for 14 days after the induction with indomethacin. The protective effect was measured based on intestinal parameters of the disease activity index, colitis score, myeloperoxidase (MPO) activity in the colon. The inflammation biomarkers were quantified by ELISA in the rat colon. Further, activity was ascertained by histopathology. Pro-inflammatory functions IL-1a, IL-1b, IL-2, TNF, INFγ, STAT3, and CCL-5 play an important role in the variation of the intestinal immune system. Wedelolactone showed significantly decreased Disease activity index, Colitis score, Myeoloperoxidase activity. Expression of pro-inflammatory was increased in indomethacin-induced groups and was significantly suppressed in animals administered with wedelolactone at 50 mg/kg & 100 mg/kg dose (p<0.01 & p<0.001). Histological reports also revealed that treated groups have comparatively less damage than that of the induced groups. We concluded that wedelolactone showed an anti-inflammatory effect by downregulation of the IL-6/STAT3 inflammatory signaling pathway and the equilibrium production of pro-inflammatory cytokines.