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Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in
Sung-Eun Kim1, Il-Gyu Ko1, Jun-Jang Jin1
1Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Abstract:
Ischemic colitis is resulted from an inadequate blood supply to a segment or entire colon. Polydeoxyribonucleotide (PDRN), extracted from salmon sperm, has been reported to exert anti-inflammatory and anti-ischemic effects through the adenosine A2A receptor (A2AR). We investigated whether PDRN possesses therapeutic effectiveness on ischemic colitis rats. Ischemic colitis was induced by selective devascularization. The skin temperature on the ischemic colitis-induced region was determined. To assess the colonic damage score and collagen deposition, colonic tissue sections were stained with hematoxylin and eosin (H&E), and Masson trichrome staining was performed. Western blot analysis for A2AR, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, Bax, Bcl-2, and extracellular signal-regulated kinase 1/2 (ERK1/2) was performed. Skin temperature was increased and mucosal damage and collagen deposition were observed in the affected colonic tissues in the ischemic colitis rats. Expressions of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and inflammatory mediator (COX-2) were upregulated in the ischemic colitis rats. Apoptosis was increased by decreasing the ratio of Bcl-2 to Bax and by suppressing the phosphorylated form of ERK1/2 expression in the ischemic colitis rats. Treatment with PDRN alleviated mucosal damage reduced the expressions of inflammatory cytokines and COX-2 and inhibited apoptosis in the ischemic colitis rats. PDRN treatment more enhanced the expressions of A2AR and VEGF in the ischemic colitis rats. PDRN showed therapeutic effectiveness on ischemic colitis by increasing VEGF expression and inhibiting inflammatory cytokines and COX-2 through enhancing A2AR expression.
Insights
Polydeoxyribonucleotide (PDRN) effectively treats ischemic colitis in rats. This salmon sperm extract reduces inflammation and tissue damage by enhancing adenosine A2A receptor (A2AR) and vascular endothelial growth factor (VEGF) expression.
Area of Science:
- Gastroenterology
- Pharmacology
- Molecular Biology
Background:
- Ischemic colitis stems from insufficient colon blood supply.
- Polydeoxyribonucleotide (PDRN), derived from salmon sperm, exhibits anti-inflammatory and anti-ischemic properties via adenosine A2A receptor (A2AR) activation.
- The therapeutic potential of PDRN in ischemic colitis warrants investigation.
Purpose of the Study:
- To evaluate the therapeutic effectiveness of PDRN in a rat model of ischemic colitis.
- To elucidate the molecular mechanisms underlying PDRN's action in this condition.
Main Methods:
- Ischemic colitis was induced in rats via selective devascularization.
- Skin temperature, colonic mucosal damage, and collagen deposition were assessed.
- Western blot analysis was used to measure A2AR, VEGF, COX-2, TNF-α, IL-1β, IL-6, Bax, Bcl-2, and ERK1/2 expression.
- Hematoxylin and eosin (H&E) and Masson trichrome staining were performed.
Main Results:
- Ischemic colitis rats exhibited increased skin temperature, mucosal damage, and collagen deposition.
- Expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6) and COX-2 were upregulated.
- Apoptosis increased, indicated by a decreased Bcl-2/Bax ratio and suppressed p-ERK1/2.
- PDRN treatment alleviated mucosal damage, reduced inflammatory markers and COX-2, and inhibited apoptosis.
- PDRN enhanced A2AR and VEGF expression in ischemic colitis rats.
Conclusions:
- PDRN demonstrates significant therapeutic efficacy in treating ischemic colitis.
- PDRN acts by upregulating A2AR and VEGF, subsequently inhibiting inflammatory cytokines and COX-2.
- PDRN offers a promising therapeutic strategy for ischemic colitis by modulating key molecular pathways.
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