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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.

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

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