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

Abstract

Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced 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 stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced 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.

Nutrigenomics: Challenges and Opportunities

“…Curcumin H+, K + -ATPase Help in the treatment of gastric ulcers [27] IL-6,TNF-_, COX2 Reduces inflammation [28] SOCS1-3,p38MAPK Trans locates nuclear material in a different way.…”

Curcumin: A Potent Protectant against Esophageal and Gastric Disorders

“…Recent evidence indicates that curcumin can be effective as a protective substance against the formation of stress-induced gastric lesions in rats [52], in part due to the inhibition of gastric secretory activity mediated by a strong inhibitory action on H + /K + ATPase activity in parietal cells of the rat stomach. Using a chromatin immunoprecipitation assay, He et al have demonstrated that curcumin inhibited the H + /K + ATPase promoter via histone acetylation, the gene and protein expression of the gastric H + /K-ATPase α subunit, thus resulting in the rise in pH and the amelioration of stress-induced gastric ulcerogenesis [52].…”

“…Recent evidence indicates that curcumin can be effective as a protective substance against the formation of stress-induced gastric lesions in rats [52], in part due to the inhibition of gastric secretory activity mediated by a strong inhibitory action on H + /K + ATPase activity in parietal cells of the rat stomach. Using a chromatin immunoprecipitation assay, He et al have demonstrated that curcumin inhibited the H + /K + ATPase promoter via histone acetylation, the gene and protein expression of the gastric H + /K-ATPase α subunit, thus resulting in the rise in pH and the amelioration of stress-induced gastric ulcerogenesis [52]. In another study, the anti-ulcer activity of curcumin in rats exposed to either chronic stress and/or unpredictable stressors was observed simultaneously with an evident improvement in memory deficit assessed in their study by the elevated plus maze test and by the overall improvement of homeostatic functions [53].…”

Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases

“…In rat animal model, curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease by acting as a strong inhibitor of H+, K+-ATPase activity. It downregulated the acetylation of histone H3, thereby inhibiting the transcription and expression of H+, K+-ATPase gene [ 87 ]. Curcumin strongly inhibits the expression of LPS-induced inflammatory mediators along with IL-6, TNF-α and COX-2 mRNAs in macrophages via modulating the expression of cytokine signaling-1(SOCS-1 and 3) and p38 MAPKsuppressors.…”