The Influence of Medicinal and Aromatic Plants Extracts on the Antifungal Effect of Fluconazole Regarding C. Albicans and C. Tropicalis Isolated From Patients With Denture Stomatits

Abstract

Candida albicans is one of the most common and virulent representatives of Candida fungi which causes fungal lesions of the mucous membranes predominantly in people with compromised immune system. Candida resistance to classical antifungals such as polyenes, azoles, allylamines is a serious practical problem. Imidazole and triazole are the most commonly used antifungal agents for candidiasis today. Their mechanism of action lies in the inhibition of ergosterol biosynthesis which is indispensable for maintaining the structural integrity of fungal cell membranes. Activation of elimination systems is often associated with changes in the structure of fungal membranes, leading to a decrease in the supply of azoles into the fungal cell Screening of antifungal activity and synergism of antifungal activity of 166 aqueous-ethanol plant extracts with Fluconazole in relation to 2 clinical strains of Candida fungi (C.) (C. albicans and C. tropicalis) with different mechanisms of azole resistance isolated from patients with prosthetic stomatitis was conducted by means of agar diffusion method. The expressed direct antifungal activity of extracts of Calendula officinalis L. inflorescences, flowers of Limonium platyphyllum Lincz., flowers of Grataegus monogyna Jacq., roots of Potentilla repens L., the grass of Melilotus albus Medik, leaves of Peucedanum ruthenicum Bieb, leaves of Rhus coriaria L. and aerial part of Polythridum commune Hedw was determined in reference to the tested strains. Synergism of antifungal action with 1/4, 1/8 and 1/32 of Fluconazole MIC (minimal inhibiting concentration) in relation to both test strains of yeast-like Candida fungi was demonstrated by the flowers of Calendula officinalis L, aerial part of Melilotus albus Medik. The main purpose of the screening was to discriminate extracts in order to select those that would be promising for further testing by a more accurate сheckerboard titration method. The efflux mechanism of resistance to triazoles (in C. tropicalis test strain) is more susceptible to modification by biologically active compounds of medicinal plants. Regarding C. albicans test strain which combines the efflux mechanism of resistance with mutation(s) of ergosterol biosynthesis enzymes, the modifying effect of plant extracts is much less frequent and less pronounced. Therefore, it may be assumed that mutations of ergosterol biosynthesis enzymes provide high stability of the phenotypic manifestation of Candida azole resistance. Should that be the case, determining the azole resistance mechanism of Candida clinical isolates may be important for clinical practice. Combination therapy is more beneficial than monotherapy because it may provide more effective destruction or suppression of pathogens. The combined action of synergistic agents is quite easy to achieve in case of localized superficial lesions (which occur on the mucous membranes of the prosthetic bed in candidal prosthetic stomatitis): for example, using a systemic antifungal agent and a topical agent that contains a modifier of resistance of plant origin fungi. Synergistic interactions will increase the therapeutic efficacy of drugs, reduce the likelihood of resistance occurrence or further development, and will reduce dose-related toxicity.