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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Phloretin inhibited the pathogenicity and virulence factors against Candida albicans
Na Liu1, Nan Zhang2, Shengrong Zhang1
1Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, P.R. China.
Abstract:
Oral candidiasis is one of the most common types of fungal infection caused by Candida albicans (C. albicans). The present study aims to investigate the antifungal effects of phloretin (a dihydrochalcone flavonoid) against the C. albicans pathogenicity. In this work, we treated C. albicans SC5314 with 37.28, 74.55, or 149.10 μg/mL (equivalent to 0.5×, 1× or 2× MIC) phloretin in vitro. Besides, we established a mice model of oral candidiasis by a sublingual infection of C. albicans suspension (1 × 107 colony-forming unit/mL), and mice were treated with phloretin (3.73 or 7.46 mg/mL, which were equivalent to 50× or 100× MIC) twice a day starting on day one post-infection. The results showed that the MIC of phloretin against C. albicans was 74.55 μg/mL. Phloretin exerted antifungal activity by inhibiting the biofilm formation and suppressing the yeast-to-hyphae transition upon the downregulation of hypha-associated genes including enhanced adherence to polystyrene 1, the extent of cell elongation gene 1, hyphal wall protein 1 gene, and agglutinin-like sequence gene 3. Next, phloretin repressed the secretion of proteases and phospholipases via reducing the expression of protease-encoding genes secreted aspartyl proteases (SAP)1 and SAP2, as well as phospholipase B1. Subsequently, the in vivo antifungal activity of phloretin was testified by the reverse of the enhanced lesion severity, inflammatory infiltration, and the increased colony-forming unit counts caused by C. albicans of tongue tissues in oral candidiasis mice. In conclusion, phloretin suppressed the pathogenicity and virulence factors against C. albicans both in vivo and in vitro.
Insights
Phloretin demonstrates significant antifungal effects against Candida albicans, inhibiting biofilm formation and virulence factors. This natural compound shows promise in treating oral candidiasis both in vitro and in vivo.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Oral candidiasis is a common fungal infection caused by Candida albicans.
- Candida albicans exhibits pathogenicity through various virulence factors.
- Novel therapeutic agents are needed to combat Candida albicans infections.
Purpose of the Study:
- To investigate the antifungal effects of phloretin against Candida albicans pathogenicity.
- To evaluate phloretin's efficacy in an in vitro and in vivo model of oral candidiasis.
Main Methods:
- In vitro susceptibility testing of Candida albicans SC5314 to phloretin.
- Assessment of phloretin's impact on biofilm formation and yeast-to-hyphae transition.
- In vivo efficacy study using a murine model of oral candidiasis treated with phloretin.
Main Results:
- Phloretin exhibited an Minimum Inhibitory Concentration (MIC) of 74.55 μg/mL against Candida albicans.
- Phloretin inhibited biofilm formation and yeast-to-hyphae transition by downregulating key genes.
- Phloretin repressed protease and phospholipase secretion, crucial virulence factors.
- In vivo studies showed phloretin reversed lesion severity and reduced Candida albicans load in infected mice.
Conclusions:
- Phloretin possesses significant antifungal activity against Candida albicans.
- Phloretin effectively suppresses Candida albicans pathogenicity and virulence factors in vitro and in vivo.
- Phloretin represents a potential therapeutic candidate for oral candidiasis treatment.

