An Excipient-Free Porphyra/Pyropia sp.-Derived Polynucleotide Modulates Nitrative Stress in LPS-Stimulated Macrophages and Murine Acute Lung Injury

Polydeoxyribonucleotide (PDRN) is a DNA-derived material conventionally sourced from salmon, which has prompted interest in scalable non-animal alternatives. Here, we characterized an excipient-free polynucleotide purified from cultivated Porphyra/Pyropia sp. (PS-PDRN) and examined its radical-scavenging properties and its effects on nitrative-stress-related readouts. Reference nuclear assemblies of three Bangiales species were uniformly GC-rich (65.08–71.26%), in contrast to 43.89% for Oncorhynchus keta, the source species of conventional PDRN, which places the algal origin of the material in genomic context. PS-PDRN showed negligible DPPH radical scavenging but dose-dependent ABTS radical-cation scavenging, a profile shared with salmon-derived PDRN and distinct from the pre-purification intermediate. In LPS-stimulated RAW 264.7 macrophages, 50 µg/mL PS-PDRN raised nitrite to 133% and lowered nitrate to 85% of the LPS group, increasing the nitrite-to-nitrate partitioning ratio, and lowered 3-nitrotyrosine to 77% while iNOS protein (119%) and the total S-nitrosothiol pool (97%) were maintained and NADPH oxidase activity was unchanged. In murine LPS-induced acute lung injury, PS-PDRN lowered lung 3-nitrotyrosine to 53% of the LPS group, whereas lung iNOS protein remained at 95% and Nos2 at 67%, Hmox1 rose to 148%, and total SOD activity exceeded the LPS level. These preliminary findings show that the purified Porphyra/Pyropia sp.-derived polynucleotide has a radical-scavenging profile distinct from its pre-purification material and lowers protein nitration without proportionate suppression of iNOS-related readouts. They support further evaluation of cultivated Porphyra/Pyropia sp. as a non-animal source of PDRN-class polynucleotides and provide a basis for mechanistic, manufacturing, and translational validation.