Exploration of novel costunolide derivatives bearing indole/indoline as anti-ulcerative colitis agents by targeting JAK2-STAT3 pathways.

Ulcerative colitis (UC) is a kind of hard to cure chronic inflammatory disease. In present work, a series of new costunolide derivatives bearing indole/indoline have been prepared, and anti-inflammatory activities and mechanism have been tested. The results indicated that costunolide derivatives displayed good inhibition of NO generation. The in vivo studies showed that 4c exerted good protective effects in DSS-induced UC mice model by inhibiting the expression of IL-17 A and IL-17F, reducing the infiltration of immune cells, and inhibiting the phosphorylation of JAK2-STAT3 tyrosine residues. Therefore, new costunolide derivatives could be considered as potential JAK2/STAT3 pathway modulator for treatment of UC.