Topical Eugenol Successfully Treats Experimental <b><i>Candida albicans</i></b>-Induced Keratitis

Abstract

Purpose: To determine the efficacy of eugenol for the treatment of Candida keratitis in an experimental model. Methods: The in vitro antifungal activity of eugenol and fluconazole was tested against C. albicans strains via the microbroth dilution method. An experimental model of Candida albicans keratitis was used. Rabbits were classified into those that received no treatment (control; group 1) and those that started eugenol treatment immediately (group 2) or after 4 days (group 3) of keratitis induction (n = 12–16 rabbits/group). The 2 treatment groups were assigned to 50 μL of 4 mg/mL eugenol drops hourly for 15 days, while the control group received saline. Corneal penetration of eugenol was measured using HPLC, and corneal toxicity was evaluated clinically and histopathologically. Results: The in vitro minimum inhibitory concentrations of eugenol and fluconazole against C. albicans were 2 and > 0.4 mg/mL, respectively. A 4-mg/mL preparation of eugenol in propylene glycol was the maximum nontoxic dose on rabbit corneas as suggested by clinical and histopathologic findings. At least 75% of all eugenol-treated eyes recovered from keratitis, with improvement in the remaining 25% of the eyes compared to controls. Conclusions: Eugenol can act as a natural, safe, and effective treatment for fungal keratitis, regardless of whether treatment is started immediately or after 4 days of keratitis induction.

Production of eugenol from fungal endophytesNeopestalotiopsissp. andDiaporthesp. isolated fromCinnamomum loureiroileaves

“…Diffusion of these organic compounds soluble in ethyl acetate through the microbial membranes results in alterations of membrane fluidity and permeability, disruption of membrane-embedded proteins, inhibition of respiration, and alteration of ion transport processes (Trombetta et al, 2005). The antimicrobial activities of both crude extracts may be attributed to the presence of high concentration of eugenol as reported previously (Devi et al, 2010; Shah, Davidson & Zhong, 2013; Hassan et al, 2018). In addition, the high concentration of other constituents, such as myristaldehyde (Xiangwei et al, 2006), lauric acid (Nakatsuji et al, 2009), caprylic acid (Kim & Rhee, 2016), may be also correlated to the observed antimicrobial activity.…”

Optimal Design of Novel Microemulsions-Based Two-Layered Dissolving Microneedles for Delivering Fluconazole in Treatment of Fungal Eye Infection

“…The mechanism of the azoles group is based on blocking the synthesis of ergosterol and the cytochrome P450 dependent enzyme in the plasma membrane; thus, the delivery of the azole drug into the target site presented the inhibition of fungal growth [ 51 ]. Moreover, eugenol had potent antifungal activity against C. albicans from the phenolic hydroxyl group in the eugenol structure to disrupt the plasma membrane [ 52 ]. Therefore, eugenol provided a synergic effect with FLUZ to kill C. albicans by enhancing FLUZ solubility and antifungal activity.…”

Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species

“…Eugenol or 2-methoxy-4-[2-propenyl] phenol, a phenolic aromatic compound mainly derived from Cinnamomum and clove EO, is a natural microbiocidal compound belonging to the phenylpropanoid class of organic compounds and has been used for a long time as an analgesic in dentistry ( Hassan et al, 2018 ; Wijesinghe et al, 2021 ). Eugenol can be synthesized by guaiacol allylation with allyl chloride or produced through a biotransformation process that involves microorganisms such as Bacillus cereus , Corynebacterium spp., and Escherichia coli ( Abrahão et al, 2013 ).…”

“…Eugenol can be synthesized by guaiacol allylation with allyl chloride or produced through a biotransformation process that involves microorganisms such as Bacillus cereus , Corynebacterium spp., and Escherichia coli ( Abrahão et al, 2013 ). Eugenol also has anesthetic, neuroprotective, antidiabetic, insecticidal, analgesic, anti-inflammatory, and antifungal properties, which makes it a versatile natural ingredient that helps prevent and cure various disorders ( Kozam, 1977 ; Reddy and Lokesh, 1994 ; Hassan et al, 2018 ; Nisar et al, 2021 ). Eugenol exhibits significant antifungal activity against various fungal species, including the dermatophytes Aspergillus and Candida , primarily due to damage to the fungal cell envelope and inhibitory action against biofilm communities and various virulence factors ( Chami et al, 2005 ; Hassan et al, 2018 ).…”

“…Eugenol also has anesthetic, neuroprotective, antidiabetic, insecticidal, analgesic, anti-inflammatory, and antifungal properties, which makes it a versatile natural ingredient that helps prevent and cure various disorders ( Kozam, 1977 ; Reddy and Lokesh, 1994 ; Hassan et al, 2018 ; Nisar et al, 2021 ). Eugenol exhibits significant antifungal activity against various fungal species, including the dermatophytes Aspergillus and Candida , primarily due to damage to the fungal cell envelope and inhibitory action against biofilm communities and various virulence factors ( Chami et al, 2005 ; Hassan et al, 2018 ). As a result, scientists are interested in using eugenol to suppress Candida biofilm communities and various cellular pathways of these fungi.…”