Elsevier

Archives of Oral Biology

Volume 76, April 2017, Pages 76-83
Archives of Oral Biology

Review
Review of flavonoids: A diverse group of natural compounds with anti-Candida albicans activity in vitro

https://doi.org/10.1016/j.archoralbio.2016.08.030Get rights and content

Highlights

  • Flavonoids are a subdivision of polyphenols, a versatile class of natural compounds that represent secondary metabolites from higher plants with several reported protective activities, such as antifungal.

  • Subclasses of flavonoids include: chalcones, flavones, isoflavones, flavanols, flavanones, flavonols, and anthocyanidins.

  • The antifungal activity of flavonoids against C. albicans in vitro were reported in the literature, among potent compounds were quercetin and myricetin (flavonols), baicalein (flavones), catechins (flavanols), and carvacrol (chalcones).

  • Mechanisms of action for antifungal effects of flavonoids included inhibition of efflux pump and induction of apoptosis (baicalein and sedonan A), cell wall damage (catechins), and cytoplasmic membrane disruption (carvacrol).

  • Plasma membrane transporters play a critical role in binding of flavonoids to plasma membrane and hence determine the bioavailability of flavonoids, applied as xenobiotics.

Abstract

Flavonoids are a subdivision of polyphenols, a versatile class of natural compounds that represent secondary metabolites from higher plants and are abundant in human diet. Various protective effects of flavonoids have been reported, including antimicrobial and antifungal activities. Due to the nature of oral candidiasis and the increased use of antifungal agents, several drug-resistant strains have emerged making it impractical to rely on one standard therapeutic regime. The aim of this review is to summarize the antifungal activity of some examples of the major subclasses of flavonoids in pure extract forms against C. albicans in vitro, as reported in literature over the past 10 years (2004–2015). In addition, this review outlines the potential mechanism of actions of flavonoids studied in vitro, which may contribute to a better understanding of flavonoids as multi-targets agents in the treatment and/or prevention of oral candidiasis in clinical settings.

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.

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