Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptors.It is DNA derived from a controlled purification and sterilization process of the sperm of Oncorhynchus mykiss (Salmon Trout). PDRN is a well-known stimulator of cell growth that that accelerates cell proliferation and can help with the regeneration of skin and tissue. Due to 95% similarity between human DNA and PDRN, It is proven to be safe and effective.
Effects of polydeoxyribonucleotides (PDRN) on wound healing: Electric cell-substrate impedance sensing (ECIS)
Polydeoxyribonucleotides (PDRN) have been explored as an effective treatment for tissue repair in peripheral artery occlusive disease, diabetic foot ulcers, and eye lotion. We report on the effect of polydeoxyribonucleotides (PDRN) on wound healing by using the electric cell-substrate impedance sensing (ECIS) system and viability testing. Human osteoblasts (U2OS) and primary human dermal fibroblasts (HDF) were used to study the effect of PDRN on migration and proliferation. ECIS allowed the creation of a wound by applying high current, and then monitoring the healing process by measuring impedance in real time. The traditional culture-insert gap-closure migration assay was performed and compared with the ECIS wound assay. PDRN-treated U2OS and HDF cells affected cell motilities to wounding site. Viability test results show that HDF and U2OS proliferation depended on PDRN concentration. Based on the results, a PDRN compound can be useful in wound healing associated with bone and skin.
PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation
Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/β-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a "dual mode" of action: NF-κB inhibition and Wnt/β-catenin stimulation.
Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers
Peripheral arterial occlusive disease (PAOD) of lower extremities is becoming more prevalent worldwide. The general prognosis is particularly negative with a high prevalence of coronary heart disease and cerebrovascular disease. Diabetic foot ulcers occur in 15% of all the patients with diabetes and proceed to lower-leg amputations. In diabetic ulcers, wound healing is impaired because of delayed angiogenesis. In both pathological conditions, therapeutic angiogenesis using angiogenic growth factors, particularly Vascular Endothelial Growth Factor VEGF, is expected to be a valuable treatment. The most used approaches are based on VEGF local delivery or gene therapy, but they failed to meet the expected primary goals of therapy. Adenosine receptor stimulation can induce VEGF expression in many types of cells and this may be achieved by stimulating the A(2A) or A(2B) receptor or both, following the signalling pathways activated by hypoxia. Polideoxyribonucleotide (PDRN) is obtained from sperm trout by an extraction process. The compounds hold a mixture of deoxyribonucleotides polymers with chain lengths ranging between 50 and 2000 bp. PDRN is able to stimulate VEGF production during pathological conditions of low tissue perfusion. It likely acts through the stimulation of A(2A) receptors. Furthermore, acute and chronic toxicity studies showed a good safety profile. PDRN has been shown to be effective in an experimental model of PAOD, hind limb ischemia, impaired wound healing and burn injury. Preliminary studies and ongoing clinical trials predict a significant therapeutic efficacy in patients. These data lead to hypothesize a role for PDRN in therapeutic angiogenesis.