Red light-mediated enhancement of the antifungal activity of Physalis angulata against Candida species.

Physalis angulata L. (Solanaceae) is widely recognized for its therapeutic applications in traditional medicine. This study evaluated the antifungal activity of P. angulata (PA) and the influence of red LED-mediated photodynamic therapy (PDT) on planktonic cells and biofilms of Candida albicans, Nakaseomyces glabratus, and Candida parapsilosis. The withanolide 4β-hydroxywithanolide E was isolated from PA, and UPLC-MS analysis of the active fraction (PA-F) in negative ion mode revealed the predominance of eleven withanolides, including aglycone and glycosylated forms belonging to the 5β,6β-epoxide and 5-ene classes. The crude PA extract showed no antifungal activity (MIC >2000 μg/mL) against the tested strains, whereas PA-F exhibited a MIC of 250 μg/mL against C. albicans and 2000 μg/mL against N. glabratus and C. parapsilosis. Notably, exposure of yeast biofilms to PA-F (250 μg/mL) followed by red LED irradiation resulted in a pronounced reduction in viable cells, reaching 4.88 ± 0.12, 4.29 ± 0.15, and 4.16 ± 0.06 log₁₀ CFU/mL for C. albicans, N. glabratus, and C. parapsilosis, respectively, indicating fungicidal activity. These findings demonstrate a light-dependent enhancement of antifungal efficacy, supporting the potential of P. angulata-derived withanolide fractions as photo-responsive agents in antifungal photodynamic strategies.