Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

ABSTRACT

Curcumin is known to possess anti­inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+­ATPase activity, the mechanism underlying the curcumin­induced inhibition of the transcription of the H+, K+­ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+­ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress­induced gastric ulcers was produced, in which the anti­ulcer effects of curcumin were examined. Curcumin­induced inhibition of the H+, K+­ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress­induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+­ATPase promoter and in the expression of the gastric H+,K+­ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+­ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+­ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.