Antifungal Annona muricata L. (soursop) extract targets the cell envelope of multi-drug resistant Candida albicans

Etnopharmacological relevance: Annona muricata L. (soursop) is traditionally used in the treatment of inflam-matory diseases, cancer, and infections caused by fungi. The therapeutic activity explored by its medicinal use is generally associated with its phytoconstituents, such as acetogenins and alkaloids. However, its potential anti-fungal bioactivity as well as its mechanism of action remains to be established. Aim of the study: To evaluate the antifungal activity of the ethanolic extract of A. muricata leaves against multidrug-resistant Candida albicans (ATCC (R) 10231).Material and methods: Phytoconstituents were detected by UFLC-QTOF-MS. The minimum inhibitory concen-tration was determined, followed by the determination of the minimum fungicidal concentration. For planktonic cells, the growth curve and cell density were evaluated. Studies to understand the mechanism of action on the cell envelope involved crystal violet permeability, membrane extravasation, sorbitol protection, exogenous ergosterol binding assay, metabolic activity, and cell viability. Furthermore, mitochondrial membrane potential was assessed.Results: Our analyses demonstrated a significant inhibitory effect of A. muricata, with the ability to reduce fungal growth by 58% and cell density by 65%. The extract affected both the fungal plasma membrane and cell wall integrity, with significant reduction of the cell viability. Depolarization of the fungal mitochondrial membrane was observed after treatment with A. muricata. Rutin, xi-anomuricine, kaempferol-3O-rutinoside, nornuciferine, xylopine, atherosperminine, caffeic acid, asimilobine, s-norcorydine, loliolide, annohexocin, annomuricin, annopentocin, and sucrose were identified as extract bioactive components.Conclusions: Our findings show that the A. muricata extract is a source of chemical diversity, which acts as a potential antifungal agent with promising application to the therapy of infections caused by C. albicans.