Adenosine A2A receptor agonist polydeoxyribonucleotide ameliorates acetic acid-induced ulcerative colitis via modulating PI3K/Akt/VEGF signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by an abnormal immune response. Polydeoxyribonucleotide (PDRN), which acts on adenosine A2A receptors (A2AR), inhibits the secretion of pro-inflammatory cytokines and exhibits anti-inflammatory effects. We aimed to elucidate the effects of PDRN on acetic acid-induced UC rats. After anesthetizing the rats, acetic acid was diluted to 5 % in 0.9 % saline and administered directly into the colon at 1.0 mL per animal. Three days after acetic acid injection, the rats in the drug treatment group were intraperitoneally injected with 0.5 mL saline containing 8 mg/kg PDRN once daily for 10 days. To determine whether the effect of PDRN was mediated by A2AR, 8 mg/kg 7-dimethyl-1-propargylxanthine (DMPX), an A2AR antagonist, was administered together with PDRN. UC induction caused colonic damage, with increases in stool score, colonic wet weight, and ulcer score. UC induction increased the expression of pro-inflammatory cytokines and activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, while the expression of cyclic adenosine-3',5'-monophosphate (cAMP) and vascular endothelial growth factor (VEGF) was decreased. PDRN treatment alleviated histological damage and colonic conditions. PDRN treatment suppressed the expression of pro-inflammatory cytokines and factors related to the PI3K/Akt pathway, while increasing the expression of cAMP and VEGF. Combined treatment with PDRN and DMPX completely abolished the effect of PDRN on UC, indicating that the action of PDRN occurs through A2AR. The present results showed that PDRN could be considered as a novel therapeutic agent for treating UC.