Antimicrobials


antioxidant properties of flavonoids – and the abundance of them in our diet – could play a key role in helping to prevent these diseases.3,7


But


it’s the anti-infective properties of flavonoids that are increasingly under the microscope, with promising results that could offer much-needed options for future drug development, and various other applications. In nature, flavonoids show the ability to inhibit spore germination of plant pathogens, leading to the hypothesis for their use as an antifungal treatment in humans.4


With the


increasing incidence of fungal infections, especially from the Candida species – which are responsible for a large number of serious infections8


– researchers are exploring the


potentials of flavonoids for new antifungal therapy options. The high flavonoid content of some natural compounds, such as propolis, has shown antifungal activity against dermatophytes and Candida species in vitro,9


while different


classes of flavonoids have been investigated further to find their potential benefits. Flavones, for example, have shown efficacy against Aspergillus flavus, which causes disease in immunosuppressed patients, while flavonols have exhibited efficacy against a range of fungal species.4 The spread of methicillin-resistant


Staphylococcus aureus (MRSA) and other multidrug-resistant bacteria is a significant health issue that is only getting worse, and shortening the life of many routine treatments.10 This is why, once again, many researchers are looking for natural – or at least plant-based – alternatives to combat this threat. Plants are resistant to many microorganisms,10


and


flavonoids are thought to be one of the main agents behind their defence. This has become increasingly documented in in vitro studies, with flavonoids extracted from various plants showing antibacterial activity.4 Isoflavonoids show positive signs of


addressing the global MRSA problem by enhancing the effects of two antibiotics – ciprofloxacin and erythromycin – against these strains.10


or bacteriostatic activity, where they induce the formation of bacterial aggregates, reducing the number of colony-forming units in viable counts.4 The antibacterial mechanism of action of


flavonoids is also being investigated, with various avenues being explored to advance novel drug development. Research into small molecule efflux system blockers is rapidly expanding, including efflux pump inhibitors (EPIs) derived from natural sources12


– namely flavonoids. The synergistic


action of isoflavonoids and antibiotics described above is thought to relate to this method. Bacteria use efflux pumps to expel antibiotics from cells, and so isoflavonoids acting as EPIs nullify this resistance mechanism, making the drug more effective.10 Other mechanisms of action are also being studied. Various findings support the hypothesis that certain flavonoids inhibit bacterial DNA synthesis and, to a lesser extent, protein and lipid synthesis.4


The inhibition of membrane


function is another likely antibacterial action. Isoflavonoids, for example, have been reported to affect cell membrane permeability, and to potentially damage membrane function.4,10


This Therefore, flavonoids could either play


a synergistic role in combination with antibiotics, a direct bactericidal function against strains,11


action has been studied in more detail in the flavonoid constituent of propolis, which caused an increase in permeability of the membrane and dissipation of the membrane potential – essential for ATP synthesis, transport of substances across the membrane and


Flavones exhibit potential antiviral activity (in synergy with flavonols) and antibacterial activity, and are likely to be one of the most powerful antioxidant classes, while flavanones exert antioxidant, anti-inflammatory and blood cholesterol-reducing effects.


bacterial motility.4 The naturally occurring antiviral activity of


flavonoids has been accepted since the 1940s, which has led to a multitude of recent studies to try and replicate this activity in humans.4 Most investigations have been on the human immunodeficiency virus (HIV), with in vitro studies showing promising signs of inhibiting HIV infection and replication.4,13


Other studies


have shown in vitro inhibitory effects against the herpes simplex virus, respiratory syncytial virus, poliovirus, Sindbis virus, coxsackie B virus, human coronavirus and rotavirus.4


The


proposed mechanism of action against many of these viruses includes the inhibition of viral polymerase or binding to nucleic acid or capsid proteins.4


SARS-CoV-2 in the spotlight The therapeutic options available to treat established viral infections are limited, which has been especially highlighted during the COVID-19 pandemic. New types of vaccines have been rolled out in record time, but there is a growing need for novel antiviral treatments for SARS-CoV-2, and many other viral families. Natural products, such as flavonoids, may therefore have a fundamental role to play in such pandemics in the future.2 The immunomodulatory and anti- inflammatory activities of flavonoids are especially of interest to COVID-19 treatment.14 A developing cytokine storm characterises severe cases of COVID-19, so the inhibition of this hyperinflammatory response is crucial to improving patient outcomes.14


Although this


thinking is theoretical, more reliable data is starting to trickle in on how flavonoids could be an effective therapeutic option. Several flavonoids have already been tested


in vitro, and show the potential to inhibit SARS- CoV-2 by targeting essential viral proteins.14 Institute for Antiviral Research at Utah State


The January 2024 I www.clinicalservicesjournal.com 61


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