Impact of Ergothioneine, Hercynine, and Histidine on Oxidative Degradation of Hyaluronan and Wound Healing

A high-molecular weight hyaluronan is oxidatively degraded by Cu(II) ions and ascorbate—the so called Weissberger biogenic oxidative system—which is one of the most potent generators of reactive oxygen species, namely (•)OH radicals. Ergothioneine, hercynine, or histidine were loaded into chitosan/hyaluronan composite membranes to examine their effect on skin wound healing in ischemic rabbits. We also explored the ability of ergothioneine, hercynine, or histidine to inhibit hyaluronan degradation. Rotational viscometry showed that ergothioneine decreased the degree of hyaluronan radical degradation in a dose-dependent manner. While histidine was shown to be potent in scavenging (•)OH radicals, however, hercynine was ineffective. In vivo results showed that the addition of each investigated agent to chitosan/hyaluronan membranes contributed to a more potent treatment of ischemic skin wounds in rabbits compared to untreated animals and animals treated only with chitosan/hyaluronan membranes.