Synergistic Activity of New Diclofenac and Essential Oils Combinations against Different Candida spp.

Antonio Rosato,Giuseppe Fracchiolla,Filippo Maggi,Filomena Corbo,Maria Lisa Clodoveo,Lara Salvagno,Sabina Sblano,Elisabetta Altini,Giuliana De Michele,Alessia Carocci

doi:10.3390/antibiotics10060688

Antonio Rosato, Giuseppe Fracchiolla + Show 8 more

Open Access

https://doi.org/10.3390/antibiotics10060688

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Abstract

According to recent studies, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have shown a good antimicrobial and antifungal activity. Their association with essential oils (EOs) could be useful for the treatment of infections caused by Candida spp. The aim of this studyis to evaluate the synergistic antifungal activity of new combinations between Diclofenac Sodium Salt (DSS), a widely used NSAID, with EOs of Mentha × piperita, Pelargonium graveolens and Melaleuca alternifolia. The in-vitro antifungal activity was determined on different Candida strains. The determination of the chemical composition of EOs was carried out by gaschromatography-massspectrometry (GC-MS). Susceptibility testing of planktonic cells was performed by using the broth microdilution assay and checkerboard methods. Minimum Inhibitory Concentrations (MIC) of DSS was in a range from 1.02 to 2.05 μg/mL reaching a MIC value of 0.05 μg/mL when combined with Pelargonium graveolens (FICI = 0.23–0.35) or Menthapiperita (FICI = 0.22–0.30) EOs. These preliminary results show thatthe combination of the EOs with DSS improves the antifungal activity on all the tested Candida strains.

Highlights

Fungal infections should not be underestimated, since their incidence in recent years has increased significantly, especially in immunocompromised patients [1]
The antifungal activity of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) is conceivably related to the inhibition of the cyclooxygenase enzymes (COX) leading to decrease the levels of prostaglandins that are known to be produced by Candida spp
We reported the effect of Diclofenac Sodium Salt (DSS) in combination with essential oils (EOs) of M

Summary

Introduction

Fungal infections should not be underestimated, since their incidence in recent years has increased significantly, especially in immunocompromised patients [1]. The activity of different drugs belonging to other therapeutic classes are being evaluated in the drugs-repositioning strategy as antimicrobials [7] Drugs such as Promazine (phenothiazine antipsychotic), Promethazine (antihistamine), Methyldopa (centrally acting antidepressant), Dobutamine (sympathomimetic) and Diclofenac (NSAIDs) have shown an interesting antimicrobial activity, and for this reason they have been defined as non-antibiotic drugs [8,9,10,11,12]. Current studies show that PGs may play a pivotal role in the regulation of eicosanoids pathway in Candida spp. and because of an impairment of their metabolism, the inhibition of PGs synthesis by Diclofenac should cause the fungus death [13,14,15] Based on this evidence, DSS could be able to reduce the infection, acting as a COX inhibitory agent for the treatment of Candida infections

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