Coriandrum sativum L. (Coriander) essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression

Abstract

Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO) known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander) leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis), as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

Figure 1. Effects on biofilm morphology.

SEM Photomicrographs (5,000x) showing Candida biofilm cells after treatment with propylene glycol (vehicle) (left-sided), essential oil from C. sativum leaves (middle-sided) and nystatin (right-sided). The most representative cell injuries were caused by the following concentrations of the EO: (A) C. albicans – MIC times 20 (312.5 µg/ml); (B) C. tropicalis – MIC times 10 (312.5 µg/ml); (C) C. krusei – MIC times 10 (156.0 µg/ml); (D) C. dubliniensis – MIC times 20 (625 µg/ml); and (E) C. rugosa – MIC times 20 (312.5 µg/ml). Nystatin was tested at MIC against all strains (see MIC values in Table 2) and the vehicle did not affect the biofilm integrity.

Figure 2. Anti-proteolytic activity.

Effect of different concentrations of the EO from C. sativum leaves and Pepstatin A (protease inhibitor) on the whole proteolytic activity of Candida albicans CBS 562 (One-way ANOVA with Tukey’s post-test, *P<0.05; ***P<0.0001). The group of untreated microorganism was considered as standard of 100% proteolytic activity.

Figure 3. Pharmacogenomic analysis.

Representative map of the pathways whose genes involved were up-regulated by the EO () and active fraction () from C. sativum. The thermometer next to each component indicates the type (red color means up-regulation) and the magnitude of the modulation of gene expression (MetaCore, Thomson Reuters).

Figure 4. Pharmacogenomic analysis.

Representative map of the pathways whose genes involved were down-regulated by the EO () and active fraction () from C. sativum. The thermometer next to each component indicates the type (blue color means down-regulation) and the magnitude of the modulation of gene expression (MetaCore, Thomson Reuters).