Possible applicability of flavonoid hesperetin for the treatment of dental biofilm-forming Candida glabrata

Biofilm formation is a key virulence factor for Candida glabrata because it forms an extracellular matrix that prevents antifungal passage, which resists antifungal agents and causes treatment failure. To overcome this, the present study aimed to investigate the therapeutic potential of phytocompounds as an alternative choice in eliminating dental biofilm-forming C. glabrata . The antifungal potential of various phytocompounds against C. glabrata was evaluated through zone of inhibition (ZOI) and minimum inhibitory concentration (MIC) studies. The antibiofilm potential of phytocompounds was evaluated against C. glabrata and confirmed through CV staining, MTT assay and CLSM analysis. The biocompatibility of hesperetin was checked by hemocompatibility test on human RBCs. Quercetin, morin, rutin, naringin, and hesperetin exhibits antifungal activity towards C. glabrata . Hesperetin shows slightly higher antifungal activity (ZOI: 14.6 ± 0.57 mm and MIC: 0.3 ± 0.01 mM) for C. glabrata , compared to other tested phytocompounds. The 100 % deadness of C. glabrata cells in biofilm was observed at 2MIC (0.6 mM) of hesperetin. Interestingly, hesperetin demonstrates acceptable level hemolysis (5 %) on RBCs up to 10 mM. These findings suggest that hesperetin is a novel natural antifungal agent capable of effectively inhibiting the biofilm-forming C. glabrata , with the potential for development into safe, phyto-based therapeutics for managing dental infections.