Hispidol ((Z)-Hispidol)

Hispidol ((Z)-Hispidol) is a potential therapeutic for inflammatory bowel disease; inhibits TNF-α induced adhesion of monocytes to colon epithelial cells with an IC50 of 0.50 µM.

Hispidol shows potent inhibitory effect (>70%) on the TNF-α-induced adhesion of monocytes to colon epithelial cells, which is one of the hallmark events leading to inflammatory bowel disease (IBD). Hispidol shows strong inhibitory activities against TNF-α-induced monocytic-colonic epithelial cell adhesion as well as LPS-induced TNF-α expression, is as an excellent candidate for IBD drug development. This inhibition of TNF-α expression by hispidol corresponds to the additional inhibitory activity against AP-1 transcriptional activity, which is another transcription factor required for high level TNF-α expression[1].

The oral administration of hispidol suppresses significantly and dose-dependently TNBS-induced rat colitis. Oral administration of hispidol suppresses TNBS-induced colitis in a dose-dependent manner. There is a significant recovery in body weight decrease and colon tissue edematous inflammation. A higher dose (30 mg/kg) of hispidol shows a similar recovery effect to that of 300 mg/kg sulfasalazine. In the colon tissues, TNBS induces a dramatic increase in the level of MPO, a biochemical marker of inflammation, which is suppressed significantly by hispidol in a dose-dependent manner[1].

[1]. Kadayat TM, et al. Discovery and structure-activity relationship studies of 2-benzylidene-2,3-dihydro-1H-inden-1-one and benzofuran-3(2H)-one derivatives as a novel class of potential therapeutics for inflammatory bowel disease. Eur J Med Chem. 2017 Sep 8;137:575-597.