MOLECULAR MECHANISMS AND EMERGING THERAPEUTIC STRATEGIES IN PHYTOPHOTODERMATITIS

Abstract

Phytophotodermatitis is an acute, non-immunological phototoxic skin reaction caused by plant-derived furocoumarins following exposure to ultraviolet A (UVA) radiation. It can produce erythema, edema, vesiculation, bullae, pain, and persistent post-inflammatory hyperpigmentation. UVA-activated furocoumarins induce DNA photoadduct formation, reactive oxygen species generation, oxidative stress, mitochondrial dysfunction, and activation of MAPK and NF-κB signaling, resulting in keratinocyte injury and inflammation. Current management is predominantly supportive, including decontamination, photoprotection, topical corticosteroids, analgesics, wound care, and treatment of hyperpigmentation. However, molecularly targeted therapies remain limited. Emerging approaches include Nrf2-mediated cytoprotection, modulation of oxidative stress and inflammatory signaling, mitochondrial protection, DNA damage response modulation, advanced photoprotective formulations, and targeted inhibition of melanogenesis. This review examines the molecular mechanisms and current and emerging therapeutic strategies for Phytophotodermatitis, highlighting potential targets for improved prevention and pharmacological management.