Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of −10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives.

Background: The increased rates of common fungal diseases are a constant challenge. Therefore, the search for plant-based compounds with antifungal activity, particularly ones against Candida species, is always relevant in the medical context. However, most of the studies have focused on screening the antifungal activity of extracts rather than isolated compounds. Based on this, we aimed to analyze and organize a comprehensive overview of the antifungal and other biological activities of isolated compounds found in Anacardiaceae family vegetal species, covering mechanisms of action and potential therapeutic applications. Results: The extracts, essential oils, and compounds are frequently assayed for anti-Candida activity using the in vitro minimum inhibitory concentration (MIC), minimum fungicide concentration (MFC), and halo inhibition assays. Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii were the most tested fungus species. Essential oils were the most used form (37% of the studies). The isolated compounds included shikimic acid, 2-hydroxy-1,8-cineole β-D-glucopyranoside, myricitrin, cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-O-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, pistagremic acid, apigenin, sakuranetin, oleanolic aldehyde, and integriside. Conclusions: Our data indicate that the compounds isolated from Anacardiaceae species show promise for developing new therapeutic antifungal drugs, mainly if we consider their other biological activities, including anti-inflammatory, antioxidant, and apoptotic effects. In this context, they may be candidates for future treatments of fungal infections, especially in combination with conventional antifungals or when used in nanostructured formulations, which may result in a new avenue of using plant extracts and isolated compounds.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Background/Objectives: Vismia guianensis is a vegetal species popularly used to treat fungal infections. This study evaluated the anti-Candida effect of V. guianensis extract after C. albicans lethal infection in Tenebrio molitor larvae and mice. Methods and Results: The chemical profile analysis of a hydroethanolic extract of the leaves of V. guianensis (EHVG) identified 14 compounds. Two sets of experiments used T. molitor larvae. To evaluate toxicity, the uninfected larvae were treated with EHVG or anthraquinone. We considered the following groups: the controls received PBS; ANFO B received amphotericin B (600 mg/mL); EHVG received the extract; and ANTQ received anthraquinone. The extract and anthraquinone resulted in low-level toxicity in the T. molitor larvae. Another set of experiments evaluated the EHVG effect during lethal infection with Candida albicans. The T. molitor larvae were treated intracelomically (ic/10 μL). Treatment with EHVG efficiently improved the survival of the larvae after lethal infection (60%), probably due to the reduction in CFUs. In the mice, the antifungal effect of EHVG was determined in three groups of immunosuppressed Swiss mice (cyclophosphamide, 50 mg/kg/ip) infected with C. albicans (1 × 10⁷ CFU/ip). The control animals were infected and untreated; the ANFO B animals were infected and treated with amphotericin B (600 µg/kg/ip); and the EHVG animals were infected and treated with the extract (5 mg/kg/orally). A SHAM group (uninfected and untreated) was also included. Survival was assessed for 5 days. The extract increased the mice’s survival (60%) and life expectancy, reducing the CFU counts in the peritoneum and blood. EHVG also increased the number of blood neutrophils and peritoneal macrophages. These systemic activities are likely associated with the presence of flavonoids in the extract. Conclusions: The beneficial effects of EHVG in lethal sepsis are related to an antifungal effect, with the number of CFUs decreasing in the larvae and the mice. In addition, EHVG showed immunological activity in the mice, considering immune cell distribution and cytokine production.