Revaprazan, a novel acid pump antagonist, exerts anti-inflammatory action against Helicobacter pylori-induced COX-2 expression by inactivating Akt signaling

Abstract

Chronic gastric inflammation developing after Helicobacter pylori (H. pylori) infection is responsible for either dyspeptic symptom relevant to gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants, especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as well as the eradication regimen. Among several mediators engaged in propagating gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be the principal one, and several prescriptions have been made for decreasing the COX-2 levels. Multiple line of evidence are available for anti-inflammatory action of PPIs beyond acid suppression, but revaprazan, a novel acid pump antagonist launched in clinic, has also been suggested to exert significant anti-inflammatory actions as much as PPI. In the current study, we hypothesized that revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti-inflammatory pharmacological actions. The changes of gastric COX-2 expression as well as responsible transcription factors were measured after H. pylori infection in the presence or absence of revaprazan. Infection of AGS cells with H. pylori induced significant up-regulation of COX-2 in time- and concentration-dependent manners, which was mediated by Akt phosphorylation. Revaprazan treatment significantly inhibited IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Additional rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted. In conclusion, revaprazan imposed significant anti-inflammatory actions on H. pylori infection beyond acid suppression.

Special Licorice Extracts Containing Lowered Glycyrrhizin and Enhanced Licochalcone A Prevented Helicobacter pylori‐Initiated, Salt Diet‐Promoted Gastric Tumorigenesis

“…Our s‐lico can be used for ameliorating gastric inflammation caused by H. pylori infection as it efficiently attenuated ROS generation and inflammatory mediator such as COX‐2 and iNOS expression under lesser adverse effects. As effective modulation of inflammation can confer the possibility of cancer prevention in diverse kinds of GI cancers associated with inflammation on their pathogenesis such as chronic atrophic gastritis, chronic reflux esophagitis, cholangitis, pancreatitis, and inflammatory bowel disease , we extended our hypothesis that long‐term administration of s‐lico can provide the chance of rejuvenating H. pylori ‐associated chronic atrophic gastritis as well as prevention of gastric tumorigenesis. Considering the link between inflammation and carcinogenesis, for instances, the pro‐inflammatory enzymes including COX‐2 and iNOS have been implicated in carcinogenesis , continuous administration of s‐lico lead to safe and efficient achievement of prevention of H. pylori ‐associated gastric tumorigenesis through ameliorating these inflammatory mediators including COX‐2.…”

A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug–Drug Interactions with Orally Administered Medications

“…Limitations of this review are that the search strategy was not replicated by a second individual, the risk for incomplete retrieval of interactions via the search strategy used, and that any additional information available after 1 August 2018 was not captured. The search strategy did not specifically include the names of the potassium-competitive acid pump antagonists revaprazan [43] and vonoprazan fumarate [44], which are approved in South Korea and Japan, respectively. Additionally, these drugs were not identified using the broad search terms, likely due to the limited number of countries in which they are approved.…”

The Anti-inflammatory Effects of Acidic Polysaccharide from Artemisia capillaris on Helicobacter pylori Infection

“…In this study, weput hypothesis that the polysaccharides from Artemisia can be used for ameliorating gastric inflammation caused by H. pylori infection as it efficiently attenuated inflammatory mediator such as COX-2 and iNOS expression. Since effective modulation of inflammation can confer the possibility of cancer prevention in diverse kinds of GI cancers associated with inflammation on their pathogenesis such as chronic atrophic gastritis, chronic reflux esophagitis, cholangitis, pancreatitis, inflammatory bowel disease, 19 we extended our hypothesis that long-term administration of the polysaccharides from Artemisia can provide the hope of chemoprevention of H. pylori -associated chronic gastritis. Considering the link between inflammation and carcinogenesis, for instances, the pro-inflammatory enzymes including COX-2 and iNOS have been implicated in carcinogenesis, 20 continuous administration of the polysaccharides from Artemisia lead to safe and efficient achievement of prevention of H. pylori -associated gastric tumorigenesis through ameliorating these inflammatory mediators including COX-2.…”