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Aims The main action of proton pump inhibitors (PPIs) is to inhibit gastric acid secretion, and PPIs are widely used to treat gastric ulcer (GU). However, if the action of promoting gastric mucosal regeneration is added, the effectiveness of GU treatment can be enhanced. Thus, in order to improve the therapeutic effect on GU, we tried to develop combination therapy promoting regeneration in injured tissue besides suppressing gastric acid secretion. Main methods Polydeoxyribonucleotide (PDRN) was selected to evaluate tissue regeneration, and pantoprazole was chosen as one of the PPIs. GU was induced by oral administration of indomethacin once a day for 7 days. Rats in drug-administered groups were intraperitoneally injected with 100 μL normal saline, containing each drug at the indicated concentration, once a day for 14 days after inducing GU. Key findings PDRN and PPI combination therapy potently improved tissue regeneration and inhibited production of pro-inflammatory cytokines. PDRN treatment with or without PPI increased the concentration of cyclic adenosine-3,5′-monophosphate (cAMP) and the ratio of phosphorylated cAMP response element-binding protein (p-CREB) to cAMP response element-binding protein (CREB). PDRN treatment with or without PPI also increased the expressions of vascular endothelial growth factor (VEGF) and adenosine A2A receptor. Significance PDRN and PPI combination therapy showed more potent therapeutic effect on GU compared to the PDRN monotherapy or PPI monotherapy. The excellent therapeutic effect of PDRN and PPI combination therapy on GU appeared by promoting regeneration of damaged tissue as well as inhibiting gastric acid secretion.

Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastric mucosal damage and gastric ulceration. Among the most commonly used NSAIDs, indomethacin upregulates mucosal tumor necrosis factor-α, which activates nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPK) to induce various pro-inflammatory mediators. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that exerts anti-inflammatory effects. In this study, we evaluated the efficacy of PDRN in the initial treatment of gastropathy against that of ecabet sodium and irsoglandin maleate, which are commonly used medications. The rats were administrated indomethacin once a day for 7 days after 24 h of fasting to induce gastropathy. Rats in the drug-treated groups were orally administrated 500 μl of distilled water containing the drug once daily for 7 days 1 h after indomethacin administration. Indomethacin administration caused mucosal damage and increased pro-inflammatory cytokine release. Both NF-κB and MAPK cascade factors were increased by indomethacin administration. PDRN therapy more potently suppressed the expressions of NF-κB and MAPK cascade factors compared to other drugs. The expression of cyclic adenosine-3′,5′-monophosphate was also increased by PDRN treatment in the indomethacin-induced gastropathy rats. These changes led to a reduction in pro-inflammatory cytokines and apoptotic factors, which ultimately promote recovery of damaged gastric tissue. Therefore, PDRN may serve as a new therapeutic option in the initial treatment of NSAIDs-induced gastropathy.