To protect the human body against environmental stress, such as UVB, a multifunctional enzymatic and antioxidant defense system is expressed in the skin. A key regulator of this pathway is the transcription factor Nrf2. Thus, we have speculated that target activation of this pathway may provide therapeutic options against oxidative stress-related disorders. A novel pharmacological Nrf2 activator (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) was synthesis and evaluated on several in vitro skin models. Human skin explants were pre-treated with the compound for 24 hr and then exposed to UVB. ROS generation was reduced significantly in SK-119 treated tissue. In addition, UVB-induced apoptosis and reduction in viability were attenuated in the epidermal layer. Importantly, Nrf2 activation reduced DNA adduct formation caused by UVB. SK- 119 had also attenuated cytokine secretion induced by both UVB and LPS. The collective results suggest that Pharmacological activation of the Nrf2 may be used as a therapeutic option in light-sensitive disorders by enhancing the endogenous protection of the skin.

Pharmacological activation of the Nrf2 pathway attenuates UVB & LPS-induced damage