Phytochemicals as Novel Antifungal Agents Against Candida species

Infections caused by Candida, including vulvovaginal candidiasis (VVC) and invasive candidiasis (IC), are a growing public health problem, exacerbated by multidrug resistance, biofilm persistence, and the limited development of antifungal drugs. In this review, we discuss plant-derived natural products with potent anti-Candida activity, specifically terpenoids, alkaloids, flavonoids, phenolics, and their nanoformulations. Many compounds, including berberine, artemisinin, thymol, eugenol, carvacrol, quercetin, catechins, lawsone, and caffeic acid, have shown the ability to modulate the fundamental mechanisms of fungal growth, which include disrupting membranes, inhibiting ergosterol biosynthesis, modulating efflux pumps, inducing oxidative stress, and biofilm inhibition. Some phytochemicals also demonstrate synergism with azoles, polyenes, and echinocandins, which can support dose reduction and restoration of resistance. Ultimately, while there is supportive preclinical evidence for anti-Candida action via the aforementioned compounds, clinical translation has been limited due to issues concerning standardization of use, pharmacokinetic variability, and toxicity issues. Some recent advances in nano-delivery systems, structural bioactivity modifications, and molecular docking studies provide a path forward when considering ways to maximize antifungal properties and improve bioavailability. This review highlights current advancements, therapeutic opportunities, and critical research gaps to accelerate the integration of phytochemicals into antifungal stewardship and device-associated infection control strategies.