Thermal-denatured PDRN exhibits increased in vitro pharmacological activities: A functional role of single-stranded DNA random coils

Abstract

Polydeoxyribonucleotide (PDRN) is a DNA-based remedy that is broadly utilized for the treatment of wounds, inflammatory diseases and other diverse disorders. The present study aimed to clarify which conformational state of PDRNs, single-stranded DNA (ssDNA) random coil or double-stranded DNA (dsDNA) helical form, was responsible for its in vitro pharmacological properties, such as antioxidant, anti-inflammatory, skin whitening and anti-wrinkling properties. A PDRN solution was subjected to thermal denaturation at a high temperature, which generated heated PDRN (PDRN-H) with augmented ssDNA random coils. Skin in vitro beneficial properties of PDRN and PDRN-H were analyzed and compared using the non-celled in vitro models. PDRN itself was shown to exhibit positive effects, such as a scavenging or inhibitory effect, in all tests done, such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS), superoxide and nitrite scavenging assays, and tyrosinase, elastase and collagenase inhibition assays. However, PDRN-H exhibited 10.3- and 1.6-fold higher activities in the DPPH and ABTS scavenging assays compared with PDRN, respectively. PDRN-H showed 2.2- and 4.7-fold higher activities in the superoxide and nitrite scavenging assays compared with PDRN, respectively. PDRN-H also displayed 2.3- and 1.8-fold higher activities compared with PDRN in the inhibition assays of L-tyrosine hydroxylase and L-DOPA oxidase activities of tyrosinase, respectively. PDRN-H was able to suppress elastase and collagenase activities and the degrees of their inhibition activities were 3.9- and 2.2-fold higher than those of PDRN, respectively. Although both PDRN and PDRN-H demonstrate in vitro beneficial properties for the skin, such as antioxidant, anti-inflammatory, skin whitening and antiwrinkle properties, PDRN-H exerts remarkably higher skin beneficial properties than PDRN due to its augmented single-stranded DNA random coils. Overall, these findings suggest that the single-stranded DNA random coils of PDRNs serve as an active player for the in vitro pharmacological properties.