Pilot studies examining cinnamon-based Nrf2 activation targeting arsenic-impairment of skin wound healing

The Pilot Project was designed to generate strong preliminary experimental evidence in human skin reconstructs and mouse skin to confirm the feasibility of cutaneous Nrf2 upregulation using topical cinnamaldehyde (CA) and to support CA-based suppression of photocarcinogenesis in a SKH1-Nrf2 wild type mouse model. Data indicate that CA causes a Keap1-C151-dependent increase in the Nrf2 half-life via blockage of ubiquitination with upregulation of a broad panel of cytoprotective Nrf2 target genes and elevation of cellular glutathione. A resulting publication likewise indicated that Nrf2-inducers could protect reconstructed human skin from sunburn. Observations also revealed that topical CA treatment upregulates Nrf2 and target gene expression (NQO1) in reconstructed human epidermis (EpidermTM, MatTek) exposed to topical CA (10 mM, 24 h) as detected by immunohistochemistry. Compelling preliminary data indicating that topical CA-based treatment (25 mM in Vanicream carrier) suppresses photocarcinogenesis in a murine solar exposure model has also been obtained.