Abstract

Current treatments for Candida albicans infection are limited due to the limited number of antifungal drugs available and the increase in antifungal resistance. Curcumin is used as a spice, food preservative, flavoring, and coloring agent that has been shown to have many pharmacological activities. Thus, this study evaluated the modulatory effects of curcumin on major virulence factors associated with the pathogenicity of C. albicans. The minimum inhibitory concentration (MIC) of curcumin against C. albicans (SC5314) was determined. Biofilm formation was quantified and the proteinase and phospholipase secretion was measured. The cytotoxicity was tested in oral fibroblast cells. A cocultured model was used to analyze the gene expression of proinflammatory cytokines (IL-1β, IL-1α, and IL-6) from host cells, as well SAP-1 and PLB-1 by RT-PCR. The MIC was between 6.25 and 12.5 µM, and the activity of proteinase enzyme was significantly decreased in biofilms treated with curcumin. However, proteinase gene expression was not downregulated after curcumin treatment. Furthermore, gene expressions of host inflammatory response, IL-1β and IL-1α, were significantly downregulated after exposure to curcumin. In conclusion, curcumin exhibited antifungal activity against C. albicans and modulated the proteolytic enzyme activities without downregulating the gene expression. In host inflammatory response, curcumin downregulated IL-1β and IL-1α gene expression.

Highlights

  • Candida albicans is a prevalent opportunistic fungus that becomes pathogenic in patients with reduced immune competence or in individuals with an imbalance of competing bacterial microflora [1,2,3]. e pathogenicity of the Candida species is attributed to critical virulence factors, such as the ability to evade host defenses, adhere to surfaces, biofilm formation, and the production of proteolytic enzymes, such as secreted aspartyl proteases (SAP) and phospholipases [4]

  • Results e minimum inhibitory concentration (MIC) for curcumin against C. albicans was in a range between 6.25 μM and 12.5 μM. e bio lm assay results showed a decrease in the mass of bio lms treated with curcumin (62.5 μM and 12.5 μM) in relation to the vehicle control (Figure 1)

  • After treatments with curcumin at 62.5 μM and 125 μM, there was a signi cant decrease (p < 0.05) in the proteinase and phospholipase enzyme activity when compared to the vehicle (Figures 2(a) and 2(b)). ere were no di erences in the expression of secreted aspartyl proteinases-1 (SAP-1) after exposure to curcumin (Figure 3(a)). e treatment with 10 μM curcumin signi cantly increased the phospholipase B-1 (PLB-1) gene expression in comparison to the vehicle

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Summary

Introduction

Candida albicans is a prevalent opportunistic fungus that becomes pathogenic in patients with reduced immune competence or in individuals with an imbalance of competing bacterial microflora [1,2,3]. e pathogenicity of the Candida species is attributed to critical virulence factors, such as the ability to evade host defenses, adhere to surfaces (on tissues and medical devices), biofilm formation, and the production of proteolytic enzymes, such as secreted aspartyl proteases (SAP) and phospholipases [4].Current treatments for C. albicans infection consist of topical and systemic pharmaceutical antifungal agents [5].Antifungal resistance has been increasing due to the limited number of antifungal treatments available and the widespread use of these drugs [6, 7]. erefore, the discovery of new and effective antifungal therapeutic agents is a necessity. Candida albicans is a prevalent opportunistic fungus that becomes pathogenic in patients with reduced immune competence or in individuals with an imbalance of competing bacterial microflora [1,2,3]. Current treatments for C. albicans infection consist of topical and systemic pharmaceutical antifungal agents [5]. Polyphenols are secondary metabolites found in many plants, which have been used for thousands years in traditional herbal remedies due to their diverse biological activities [9]. Protective effects of such flavonoids have been reported against cancer, cardiovascular diseases, diabetes, infectious disease, as well as age-linked conditions, which

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