Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans

Abstract

New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.

The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing

“…For a very long time now, PAE has been generally regarded as a safe flavoring ingredient for foods [5], and it has some hygienic functions, such as hypolipidemic action [42], protection against inflammation [43,44], and assisting in curing depression [45]. Besides, in our previous study, PAE showed an effective antifungal activity against some food-borne fungi, such as A. falvus [10], A. niger [9], and Ceratocystis fimbriata [46], with a striking inhibition of food decay, and against Candida albicans, which protects humans from candidiasis infection [44,47]. Moreover, the antifungal pathways of PAE must be partly explained.…”

Cinnamaldehyde, a Promising Natural Preservative Against Aspergillus flavus

“…We examined the apoptotic characteristics of CA-treated cells, and the results showed that CA caused the externalization of PS on the outer surface of the plasma membrane (Figure 7). DNA damage and nuclear fragmentation are typical morphological features of apoptotic cells in the late stage of apoptosis (Tian et al, 2017). It is well-known that DAPI fluorescent probes are used to detect chromatin condensation, and TUNEL staining is one of the most reliable strategies for identifying the amount of DNA fragmentation visible.…”

“…Broth microdilution methods are commonly used for in vitro antifungal assays (Tian et al, 2017). For our experiments, 80 µl of different concentrations of CA, 100 µl of potato dextrose broth (PDB), and 20 µl 5 × 10 6 spores/ml A. flavus were added to each of 10 wells.…”

“…Some scholars have suggested that phenolics can damage mitochondrial function through targeting antioxidative signal transduction and thereby inhibit pathogenic Aspergillus (Kim et al, 2004(Kim et al, , 2006. Our own previous studies have indicated that apoptosis-promoting compounds are a promising direction in the exploration for a novel antimicrobial drug, and many antifungal agents have been investigated through the apoptotic pathway, such as amphotericin B and anacardic acid (Tian et al, 2017;Qu et al, 2019). In addition, our recent research has shown that Nerol possesses an anti-A.…”

Potential role of potassium and chloride channels in regulation of silymarin‐induced apoptosis in Candida albicans

“…During apoptosis, several hallmarks, such as DNA fragmentation, cell cycle arrest, and caspase activation, are evident . Both caspase activation and DNA fragmentation were observed in the silymarin‐treated and DIDS‐pretreated cells, but not in the TEA‐pretreated cells.…”