Caffeine affords several beneficial effects on human health, acting as an antioxidant, anti-inflammatory agent, and analgesic. Caffeine is widely used in cosmetics, but its antimicrobial activity has been scarcely explored, namely against skin infection agents. Dermatophytes are the most common fungal agents of human infection, mainly of skin infections. This work describes the in vitro effect of caffeine during keratinocyte infection by Trichophyton mentagrophytes, one of the most common dermatophytes. The results show that caffeine was endowed with antidermatophytic activity with a MIC, determined following the EUCAST standards, of 8 mM. Caffeine triggered a modification of the levels of two major components of the fungal cell wall, β-(1,3)-glucan and chitin. Caffeine also disturbed the ultrastructure of the fungal cells, particularly the cell wall surface and mitochondria, and autophagic-like structures were observed. During dermatophyte–human keratinocyte interactions, caffeine prevented the loss of viability of keratinocytes and delayed spore germination. Overall, this indicates that caffeine can act as a therapeutic and prophylactic agent for dermatophytosis.

Natural plant-derived extracts are increasingly recognized for their antimicrobial, antioxidant, and anti-inflammatory properties, making them promising candidates for the prevention and/or treatment of various diseases. Camellia sinensis Azorean Black Tea (ABT) and spent coffee grounds (SCG) were selected due to their high content of bioactive compounds, including catechins, theaflavins, chlorogenic acids, and caffeine, which have demonstrated potential against microbial infections. ABT and SCG extracts were applied to the hallux (big toe) skin of healthy volunteers for 8 h. Samples were collected before and after exposure and cultured on blood agar to determine colony-forming units (CFU), which were normalized to CFU/cm² of skin. No macroscopic skin alterations, thermographic changes, or early signs of inflammation were observed following exposure to these extracts. While the humid control and ABT exposure groups exhibited increased bacterial proliferation, SCG exposure resulted in bacterial levels statistically comparable to those of the dry control, with significantly lower bacterial growth than the humid control and ABT exposure groups. Overall, these findings add to the growing evidence supporting the use of natural extracts as sustainable options for skin protection and the regulation of microbial proliferation.