Induction of oxidative stress as a possible mechanism of the antifungal action of three phenylpropanoids

Abstract

The increasing incidence of hospital-acquired infections caused by drug-resistant pathogens, host toxicity, the poor efficacy of drugs and high treatment costs has drawn attention to the potential of natural products as antifungals in mucocutaneous infections and combinational therapies. Moreover, cellular and subcellular targets for these compounds may provide better options for the development of novel antifungal therapies. Eugenol, methyl eugenol and estragole are phenylpropanoids found in essential oil. They are known to possess pharmacological properties including antimicrobial activity. Induction of oxidative stress characterized by elevated levels of free radicals and an impaired antioxidant defence system is implicated as a possible mechanism of cell death. An insight into the mechanism of action was gained by propidium iodide cell sorting and oxidative stress response to test compounds in Candida albicans. The extent of lipid peroxidation (LPO) of cytoplasmic membranes was estimated to confirm a state of oxidative stress. Activity levels of primary defence enzymes and glutathione were thus further determined. Whereas these compounds cause fungal cell death by disrupting membrane integrity at minimum inhibitory concentrations (MIC), sub-MIC doses of these compounds significantly impair the defence system in C. albicans. The study has implications for understanding microbial cell death caused by essential oil components eliciting oxidative stress in Candida. The formation of membrane lesions by these phenylpropanoids thus appears to be the result of free radical cascade-mediated LPO.

Antioxidant and Antimicrobial Activities of Clove Bud Essential Oil and Eugenol Nanoparticles in Alcohol-Free Microemulsion

“…Beside the antioxidant activity, CEO and eugenol have well established antimicrobial activity against some food pathogen and spoilage bacteria 16 . This included Salmonella typhi 17 , 18 and some fungi like Candida albicans 19 . CEO also has synergistic interaction with antibiotics against Gram negative bacteria 20 .…”

Characterization of Secondary Metabolites from Rhizopus oryzae and Its Effect on Plant Pathogens

“…Eugenol and methyl eugenol are phenylpropanoids and are known to possess antimicrobial activity, induction of oxidative stress characterized by elevated levels of free radicals and an impaired antioxidant defence system. It may be a possible mechanism of cell death (Khan et al, 2011). In additions to antifungal activtity we have also reported for the first time that the existence of Methyl Euginol in Rhizopus oryzae (Faisal and Lakshman, 2016).…”

Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans

“…Based on that, it can be stated that the mechanism of action of eugenol against C. albicans is probably not related to the degradation of fungal cell wall. Possibly, other mechanisms such as inactivation of ergosterol synthesis and production of free radicals, can be responsible for the antimicrobial effect of eugenol [28,29].…”

“…Although several studies have investigated the antifungal effect of eugenol [14,[28][29][30], the mechanisms by which eugenol induces C. albicans cell death are not completely understood yet. In this study, the osmotic protective effect of sorbitol was not present, since there was no variation in the values of MIC, similarly to a previous investigation [30].…”