ReviewReview of flavonoids: A diverse group of natural compounds with anti-Candida albicans activity in vitro
Introduction
Oral candidiasis (OC) is one of the most common fungal infections affecting the oral cavity (Das, Nightingale, Patel, & Jumaa, 2011). Candida albicans is a prevalent opportunistic human fungal pathogen that is often implicated in OC and is the most common isolated Candida specie in clinical cases of invasive fungal infections (Liu et al., 2014). C. albicans lives commensally in the gut, oral pharyngeal, genito-urinary tract and skin (Prieto, Correia, Pla, & Roman, 2016). However, pathogenicity of C. albicans and subsequent candidiasis can occur under immunocompromised conditions (Lalla, Patton, & Dongari-Bagtzoglou, 2013). For instance, the incidence of at least one episode of oral candidiasis in HIV patients is estimated to be 80–95% (Borg-von Zepelin et al., 1999). Furthermore, chemotherapy, certain medications, such as steroids and multiple antibiotic treatments, along with the use of removable dentures may predispose to OC infections (Darwazeh, Hammad, & Al-Jamaei, 2010). As a consequence of oral fungal infections, patients may have dysphagia, weight loss, or disseminated candidiasis. The disseminated forms of the disease can be life-threatening with mortality rates of 35–60% among immunocompromised, cancer patients, and those exposed to multiple treatments, such as broad spectrum antibiotics, chemotherapy, immunosuppressive therapy, and anti-retroviral therapy (Eggimann, Que, Revelly, & Pagani, 2015; Gillies et al., 2015; Tang, Liu, Lin, & Lai, 2014).
Despite the availability of broad spectrum triazoles as conventional medical therapies, the incidence of invasive candidiasis continue to increase due to antifungal resistance and the emergence of non-albicans strains of Candida, such as Candida glabrata. The azole fluconazole is currently considered the first-line of drugs that is effective against most Candida species (Lalla et al., 2013, Serpa et al., 2012). However, certain Candida species, such as C. glabrata, C. albicans, C. tropicalis, and C. parapsilosis were found to have different degrees of susceptibility and were reported to have fluconazole resistance (Sanguinetti, Posteraro, & Lass-Florl, 2015). These factors present an urgent need to evaluate novel compounds with antifungal activity. Natural compounds as sources for anti- Candida therapeutics from botanical sources have gained attention in the past decade (2004–2015) mainly because they display structural diversity and uniqueness in functional modes of action, which renders them as attractive candidates to counteract the emergence of Candida drug resistances (Kamba & Hassan, 2010; Toure, Bahi, Ouattara, Djama, & Coulibaly, 2011).
Flavonoids are a major class of natural compounds known as polyphenols, which are secondary metabolites naturally occurring in plants and found largely in foods and beverages, such as fruits, vegetables, cereals, tea, coffee, and red wine (Taveira et al., 2010). Epidemiological and some clinical studies have reported the majority of polyphenols to exhibit anti-oxidant and antimicrobial activities including antifungal, anti-viral, and anti-bacterial effects (Yigit, Yigit, & Mavi, 2009).
The aim of this review is to investigate the antifungal activities of flavonoids in vitro against Candida albicans, the most prevalent pathogen implicated in oral candidiasis; and if so, to report potential mechanism of actions. In addition, this review provides an overview of the structure, class, and origin of the diverse classes of polyphenols. To the best of our knowledge, this is the first review that outlines the antifungal activities of various subclasses of flavonoids from pure extracts against C. albicans in vitro, which may lay the foundation for translational use of such novel therapeutics in future in vivo studies as well as in clinical trials.
Section snippets
Methods
PubMed, ISI Web of Science, and Scopus were searched systematically for studies published from 2004 until 2015, primarily investigating the antifungal effects of flavonoids on Candida albicans in vitro. Keywords, such as ′flavonoids/flavones/flavonols/phenolic compounds′ and ′MIC/in vitro/Candida albicans/mechanism of action of polyphenols/classification of phenols were used in the databases search. Studies not translated or written in English were restricted using language filters. Abstracts
Results and discussion
The initial PubmMed, Web of Science, and Google Scholar search yielded 129, 192, and 90 research papers, respectively. After excluding irrelevant titles and deleting duplicates, 124 abstracts were analyzed based on specific inclusion criterias. From these 124 abstracts, 54 studies were evaluated after eliminating the remaining abstracts based on at least one exclusion criteria. A total of 24 studies that were specific on the antifungal activity of pure extracts of flavonoids against Candida
Conflict of interest
The authors state that they do not have any conflict of interest.
Acknowledgements
Declared none.
References (50)
- et al.
Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity
Phytochemistry Letters
(2008) - et al.
Urban propolis from San Juan province (Argentina): Ethnopharmacological uses and antifungal activity against Candida and dermatophytes
Industrial Crops and Products
(2014) - et al.
HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases
Journal of Investigative Dermatology
(1999) - et al.
Epidemiology, clinical characteristics, and outcome of candidemia: Experience in a tertiary referral center in the UK
International Journal of Infectious Diseases
(2011) - et al.
Preventing invasive candida infections. Where could we do better?
Journal of Hospital Infection
(2015) - et al.
Chapter 98—Cancer preventive effects of green tea polyphenols
- et al.
Chapter 86—Modulation of drug-Metabolizing enzymes and transporters by polyphenols as an anticarcinogenic effect
Chapter 73—Pharmacology of polyphenols in cardiac remodeling: Potential biological mechanisms
- et al.
Pharmacological properties and protein binding capacity of phenolic extracts of some Venda medicinal plants used against cough and fever
Journal of Ethnopharmacology
(2012) - et al.
Synergistic effects of tea catechin epigallocatechin gallate and antimycotics against oral Candida species
Archives of Oral Biology
(2015)
Screening of a polar extract of Paeonia rockii: Composition and antioxidant and antifungal activities
Journal of Ethnopharmacology
Chapter 41—Uptake and metabolism of dietary proanthocyanidins
Antifungal dibenzofuran bis(bibenzyl)s from the liverwort Asterella angusta
Phytochemistry
Chapter 40—Bioavailability and metabolism of citrus fruit beverage flavanones in humans
Chemical compositions and antimicrobial activities of four different Anatolian propolis samples
Microbiological Research
Chapter 5— biological activities of polyphenols from grapes
Bioactive flavonoids from Kaempferia parviflora
Fitoterapia
Chapter 37—Bioavailability of flavonoids: The role of cell membrane transporters
Polyphenols: A diverse class of multi-target anti-HIV-1 agents
Current Drug Metabolism
Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae)
BMC Complementary and Alternative Medicine
Fungal ABC transporter-associated activity of isoflavonoids from the root extract of Dalea formosa
Journal of Natural Products
In vitro activity of 23 tea extractions and epigallocatechin gallate against Candida species
Medical Mycology
The relationship between oral hygiene and oral colonization with Candida species in healthy adult subjects
International Journal of Dental Hygiene
Phenolic compounds from Baseonema acuminatum leaves: isolation and antimicrobial activity
Planta Medica
The effect of zuccagnia punctata, an argentine medicinal plant, on virulence factors from Candida species
Natural Product Communications
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2022, Colloids and Surfaces B: BiointerfacesCitation Excerpt :Based on these interactions with biomolecules, polyphenols have shown to possess broad spectrum antibacterial and antifungal properties by cell wall and cell membrane interactions, inhibition of enzymes and complexation of ions vital for regular cell metabolism [23,24]. Recent studies have demonstrated that these inhibitory effects also reduce the growth and biofilm formation of bacteria and fungi related to oral infections [25–28]. Particularly the virulence of C. albicans is affected by phenolic compounds via suppression of quorum sensing and hyphae formation of the fungal cells [27,29].