Abstract
Candidiasis is the most common fungal infection among immunocompromised patients. Its treatment includes the use of antifungals, which poses limitations such as toxicity and fungal resistance. Plant-derived extracts, such as Punica granatum, have been reported to have antimicrobial activity, but their antifungal effects are still unknown. We aimed to evaluate the antifungal and antiviral potential of the ethyl acetate fraction of P. granatum (PgEA) and its isolated compound galloyl-hexahydroxydiphenoyl-glucose (G-HHDP-G) against Candida spp. In silico analyses predicted the biological activity of G-HHDP-G. The minimum inhibitory concentrations (MIC) of PgEA and G-HHDP-G, and their effects on biofilm formation, preformed biofilms, and phospholipase production were determined. In silico analysis showed that G-HHDP-G has antifungal and hepatoprotective effects. An in vitro assay confirmed the antifungal effects of PgEA and G-HHDP-G, with MIC in the ranges of 31.25–250 μg/mL and 31.25 ≥ 500 μg/mL, respectively. G-HHDP-G and PgEA synergistically worked with fluconazole against planktonic cells. The substances showed antibiofilm action, alone or in combination with fluconazole, and interfered with phospholipase production. The antifungal and antibiofilm actions of PgEA and G-HHDP-G, alone or in combination with fluconazole, in addition to their effects on reducing Candida phospholipase production, identify them as promising candidates for therapeutics.
Highlights
The incidence of fungal infections is increasing considerably in humans, due to the indiscriminate use of antibiotics, immunosuppressants, and increased use of invasive procedures, such as catheters
The biological activity spectra of G-HHDP-G were determined using an online version of Prediction of Activity Spectra for Substances (PASS) software
Several activities were predicted for G-HHDP-G, including anti-infective, antioxidant, hepatoprotective, antiinflammatory, immunostimulant, and antifungal
Summary
The incidence of fungal infections is increasing considerably in humans, due to the indiscriminate use of antibiotics, immunosuppressants, and increased use of invasive procedures, such as catheters These infections can be debilitating, persistent, and result in costly treatments. Candida spp. are commonly associated with diseases in humans, such as oral and vulvovaginal candidiasis, skin infections, and onychomycosis. These infections may occur even in immunocompetent hosts [4,5], when predisposing factors are present (age, antibiotic use, sexual activity, diabetes mellitus, and idiopathic causes), resulting in the possible need for prolonged treatments that may cause recurrences and generation of resistant species [6,7]
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