Allergic potential & molecular mechanism of skin sensitization of cinnamaldehyde under environmental UVB exposure

Fragrance, a key ingredient in cosmetics, often triggers skin allergy causes rashes, itching, dryness, and cracked or scaly skin. Cinnamaldehyde (CA), derived from the bark of the cinnamon tree, used as a fragrance and is a moderate skin sensitizer. CA exhibits strong UVB absorption, its allergic potential and the molecular mechanisms underlying skin sensitization under UVB exposure remain largely unexplored. To investigate the allergic potential and molecular mechanisms of CA-induced skin sensitization under ambient UVB radiation, we employed various alternative in-silico, in-chemico and in-vitro tools. CA under ambient UVB isomerizes from trans to cis CA after 1hr of exposure. Furthermore, DPRA assay and docking with simulation studies demonstrated the enhanced allergic potential of cis-CA. Additionally, our study evaluated intracellular ROS levels and the expression of Nrf2, Catalase, and MMP-2, and 9 in KeratinoSens cells, showing significant upregulation under UVB exposure in the presence of CA. Moreover, our findings indicate that CA activates THP-1 cells co-stimulatory surface marker (CD86) via the activation of intracellular ROS, phagocytosis, and genes of the TLR4 pathway. These insights into the mechanisms uncovered by our study are crucial for managing triggers of allergic skin diseases caused by fragrance use and concurrent exposure to environmental UVB/sunlight.