Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water-soluble dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant antioxidant, anti-inflammatory and immunomodulatory activities through beneficial modulation of several significant inflammatory cytokines in vitro and in vivo. We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be non-toxic, non-teratogenic and readily distributed in the body of mice. Moreover, it significantly accelerates excisional wound healing, reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and attenuates age-associated oxidative stress in skin, demonstrating both skin regenerative and geroprotective properties of RM191A. [Display omitted] •RM191A is a Cu3+ containing coordination complex with 10-fold higher superoxide quenching activity compared to superoxide dismutase.•RM191A exhibits potent antioxidant, anti-inflammatory and immunomodulatory properties in vitro and in vivo.•RM191A protects human skin explants against UV-induced oxidative stress and DNA damage.•RM191A is non-toxic, non-teratogenic and readily bioavailable in mice.•RM191A promotes wound healing, and attenuates TPA-induced inflammation as well as age-associated oxidative stress in mouse skin.