A bis-resorcinol resveratrol congener prevents indomethacin-induced gastric ulceration by inhibiting TNF-α as well as NF-κB and JNK pathways

Abstract

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3′,5,5′-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been established using a mice model. HST-1 reversed the adverse effects of IND on several inflammatory (myeloperoxidase, cytokines, adhesion molecules etc.) and ulcer-healing (cyclooxygenases, prostaglandin, growth factors and their receptors etc.) parameters in mice. More importantly, HST-1 down-regulated TNF-α and the TNF-α-mediated activation of NF-κB and JNK/MAPK pathways that are the key determinants in the IND-gastropathy. The effect of HST-1 on all these factors was significantly better than that of Resv, misoprostol, and omeprazole. HST-1 also did not induce small intestinal mucosal injury, unlike some of the proton pump inhibitors. On the other hand, Resv reduced activation of the prosurvival ERK1/2 pathway that may explain its contraindicative property in the gastrointestinal tract.

Keywords:

• Angiogenesis
• gastric ulcer
• indomethacin
• inflammatory modulators
• NSAID

Acknowledgements

SC gratefully acknowledges Department of Atomic Energy, Government of India for the award of Raja Ramanna Fellowship.

Disclosure statement

No potential conflict of interest was reported by the authors.