Polysaccharide PAP55-1-1 derived from Periplaneta americana promotes wound healing via the COX-2/PGE2/HIF-1α pathway

Wound healing disorders are a major clinical problem. Periplaneta americana has been used by ethnic minorities in Southwest China, for skin wounds and ulcers, showing tissue-repair potential. However, the structure of its polysaccharides and how they promote healing remain unclear.

The objective of this study was to isolate an active polysaccharide from Periplaneta americana, characterize its structure, and investigate its wound-healing mechanism of action.

The active polysaccharide PAP55-1-1 was extracted using water extraction, alcohol precipitation, and the Sevage method. Its structure was characterized by FT-IR, molecular weight analysis, monosaccharide composition, methylation, and NMR. Mechanisms were studied via Western blotting, Co-IP, immunofluorescence, and metabolomics. A third-degree burn mouse model was established and wound-healing effects were evaluated using H&E, Masson, and immunohistochemical staining.

A 44.28 kDa homogeneous heteropolysaccharide, designated PAP55-1-1, was isolated and purified from Periplaneta americana. It was composed of glucose, galactose, mannose, N-acetylgalactosamine, and N-acetylglucosamine, linked by glycosidic bonds, including α-Manp-(1→, α-Galp-(1→, →2)-β-Manp-(1→, →3)-β-Glcp-(1→, →4)-α-GalpNAc-(1→, →3)-β-Galp-(1→, →6)-α-GlcpNAc-(1→, →3,4)-α-Glcp-(1→, →2,6)-α-Manp-(1 → . In vitro experiments revealed that PAP55-1-1 activates the arachidonic acid metabolic pathway, upregulates COX-2 expression, and promotes downstream metabolite production. The resulting PGE2 stabilizes HIF-1α and facilitates its nuclear translocation, thereby enhancing the transcriptional expression of target genes including VEGF, GLUT1 and EPO. In vivo studies indicated that PAP55-1-1 accelerated wound healing by enhancing re-epithelialization and collagen deposition, as well as by upregulating the expression of HIF-1α, CD31, and VEGF at the wound site.

The findings demonstrated that it promotes wound healing by regulating the COX-2/PGE2 pathway to stabilize HIF-1α, and upregulates VEGF, CD31, and HIF-1α expression, which shows that PAP55-1-1 is a potential candidate drug for future burn wound healing.