Effect of Perillaldehyde on Prophylaxis and Treatment of Vaginal Candidiasis in a Murine Model

Abstract

Vulvovaginal candidiasis is a common fungal infection afflicting women which is primarily caused by the yeast Candida albicans ( C. albicans ). It is imperative to introduce new drug classes to counter this threat due to the continuous emergence of drug-resistant cases in recent years. The purpose of this study was to clarify the in vivo antifungal activity of perillaldehyde (PAE) against C. albicans and to prove that PAE is a promising candidate for the control of vaginal candidiasis. An animal model of vaginitis was developed to demonstrate the therapeutic and preventive effects of PAE on vaginal candidiasis, and these were evaluated through fungal and histopathological examinations. In clarifying the mechanism of PAE, standard hematological test results indicated that white blood cells (WBC) were elevated abnormally in mice infected with C. albicans , whereas when the mice were treated with various concentrations of PAE, the number of WBC in the blood was reduced. Flow cytometry was used to detect the populations of neutrophils, macrophages and CD4 T cells in the vaginal tissue of the mice. PAE was found to reduce these immune cells, which all play a key role in the inflammatory response, and the related interleukin and pro-inflammatory cytokines, including IL-17, IL-22 and TNF-α. These were detected using ELISA. Finally, we detected the expression levels of E-cadherin in the PAE treatment mouse group and discovered that it had recovered to its normal levels, but in the infection mouse group, the E-cadherin expression was clearly suppressed by the presence of C. albicans . Our data demonstrated that PAE targets these cytokines and possesses the ability to fight the fungal infection while also reducing the levels of the inflammatory factors identified. Our results demonstrated that PAE has a significant preventative and therapeutic effect on vaginal candidiasis and is a potential candidate for the treatment of vaginal Candida infections.

Perillaldehyde AmelioratesAspergillus fumigatusKeratitis by Activating the Nrf2/HO-1 Signaling Pathway and Inhibiting Dectin-1-Mediated Inflammation

“…Neutrophils play a crucial role in the inflammatory response during the corneal antifungal immune response, whereas excessive neutrophil infiltration often results in severe damage to corneal tissue, which is detrimental to fungal clearance. 39 – 41 A previous study in the mouse model of Candida albicans ( C. albicans ) vaginitis have confirmed that as the PAE concentration increased, the neutrophil counts in the mouse vaginal tissue decreased significantly, and the tissue integrity was gradually restored 42 ; Uemura reported that PAE can reduce the infiltration of inflammatory cells in colitis intestinal epithelial tissue, 17 suggesting that PAE can exert anti-inflammatory effects by inhibiting neutrophils recruitment to the corneal stroma in FK.…”

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

“…PAE seems to be a very attractive antifungal agent used for food storage. 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].…”

Cinnamaldehyde, a Promising Natural Preservative Against Aspergillus flavus

“…Nevertheless, traditional antifungal drugs have continuously posed problems, which include the increasingly serious problem of drug resistance, the toxicity of the chemical antifungal compounds, drug interactions, and the high costs. Research into new antifungal agents needs to be carried out urgently because of the drug resistance and the toxicity of the compounds currently available (Sarkar et al, 2014;Qu et al, 2019). Consequently, increasing numbers of scientists are exploring novel natural products from medicinal plants such as Geraniol and Citral in an attempt to solve the question of fungal drug resistance and with consideration for the natural low toxicity and high antifungal activity of these products (Atanasov et al, 2015;Tang et al, 2018).…”

“…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.…”