In vitro activities of carvacrol, cinnamaldehyde and thymol against Candida biofilms

Miranda-Cadena, Katherine; Marcos‐Arias, Cristina; Mateo, Estíbaliz; Aguirre‐Urízar, José Manuel; Quindós, Guillermo; Eraso, Elena

doi:10.1016/j.biopha.2021.112218

Cited by 37 publications

(27 citation statements)

References 36 publications

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“…Hyphae assays and SEM results showed that α-methyl and trans -4-methyl cinnamaldehydes inhibited C. albicans filamentation markedly more than trans -cinnamaldehyde and that observed in non-treated controls ( Figures 2 , 3C ). Interestingly, trans -cinnamaldehyde at 50 μg/mL had no effect on biofilm formation by C. albicans DAY185 or ATCC 10231, which contrasts with reports ( Ying et al, 2019 ; Miranda-Cadena et al, 2021 ) that it is effective against different strains of C. albicans , and suggests trans -cinnamaldehyde inhibits biofilm formation at higher concentrations. These results concur with the findings of Taguchi et al (2013) , who concluded cinnamaldehyde acts against C. albicans in two different ways, that is, by inhibiting mycelial growth and killing activity by causing membrane damage.…”

Section: Discussioncontrasting

confidence: 91%

“…Trans -cinnamaldehyde is a yellow oil with a sweet taste and the odor of cinnamon and is primarily used as a flavoring agent as well as used in medical products, cosmetics, and perfumes ( Brackman et al, 2008 ; Doyle and Stephens, 2019 ). Furthermore, trans -cinnamaldehyde has also been documented to have antibiofilm and anti-quorum sensing activity against Vibrio harveyi ( Niu et al, 2006 ), enterohemorrhagic and uropathogenic Escherichia coli strains ( Kim et al, 2015 ; Kot et al, 2015 ), methicillin-resistant Staphylococcus aureus strains ( Kavanaugh and Ribbeck, 2012 ; Kot et al, 2018 ), Pseudomonas aeruginosa ( Kavanaugh and Ribbeck, 2012 ), Pseudomonas fluorescens ( Li et al, 2018 ), Cronobacter sakazakii ( Amalaradjou and Venkitanarayanan, 2011 ), Streptococcus pyogenes ( Beema Shafreen et al, 2014 ), Salmonella typhimurium ( Silva et al, 2018 ), and against the pathogenic fungus C. albicans ( Ying et al, 2019 ; Miranda-Cadena et al, 2021 ). In addition, cinnamaldehyde analogs are known to have an array of bioactivities, which include antibacterial ( Firmino et al, 2018 ), antifungal ( Da Nobrega Alves et al, 2020 ), antiviral ( Hayashi et al, 2007 ), antiulcer ( Tabak et al, 1999 ), antioxidant ( Mathew and Abraham, 2006 ), antidiabetic ( Im et al, 2014 ), anti-inflammatory ( Srisook et al, 2019 ), anticancer ( Fang et al, 2004 ) activities and insecticidal ( Cheng et al, 2009 ; Lu et al, 2020 ), larvicidal ( Cheng et al, 2004 ), nematicidal ( Ferreira Barros et al, 2021 ), and anthelmintic ( Williams et al, 2015 ) effects.…”

Section: Introductionmentioning

confidence: 99%

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Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

et al. 2022

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Cinnamaldehyde has a broad range of biological activities, which include antibiofilm and anthelmintic activities. The ever-growing problem of drug resistance and limited treatment options have created an urgent demand for natural molecules with antibiofilm and anthelmintic properties. Hence, we hypothesized that molecules with a scaffold structurally similar to that of cinnamaldehyde might act as dual inhibitors against fungal biofilms and helminths. In this regard, eleven cinnamaldehyde analogs were tested to determine their effects on fungal Candida albicans biofilm and nematode Caenorhabditis elegans. α-Methyl and trans-4-methyl cinnamaldehydes efficiently inhibited C. albicans biofilm formation (>90% inhibition at 50 μg/mL) with minimum inhibitory concentrations (MICs) of ≥ 200 μg/mL and 4-bromo and 4-chloro cinnamaldehydes exhibited anthelmintic property at 20 μg/mL against C. elegans. α-Methyl and trans-4-methyl cinnamaldehydes inhibited hyphal growth and cell aggregation. Scanning electron microscopy was employed to determine the surface architecture of C. albicans biofilm and cuticle of C. elegans, and confocal laser scanning microscopy was used to determine biofilm characteristics. The perturbation in gene expression of C. albicans was investigated using qRT-PCR analysis and α-methyl and trans-4-methyl cinnamaldehydes exhibited down-regulation of ECE1, IFD6, RBT5, UCF1, and UME6 and up-regulation of CHT4 and YWP1. Additionally, molecular interaction of these two molecules with UCF1 and YWP1 were revealed by molecular docking simulation. Our observations collectively suggest α-methyl and trans-4-methyl cinnamaldehydes are potent biofilm inhibitors and that 4-bromo and 4-chloro cinnamaldehydes are anthelmintic agents. Efforts are required to determine the range of potential therapeutic applications of cinnamaldehyde analogs.

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Section: Discussioncontrasting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

et al. 2022

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“…The findings of a recently published study also demonstrated severe antifungal function for cinnamaldehyde against Candida species isolated from patients with oral candidiasis. Further, cinnamaldehyde lowered the biomass and metabolic activity of mature biofilm ( Miranda-Cadena et al., 2021 ). Collectively, the biofilm biomass reduction could play a key role in controlling MDR infections as biofilms are a source for dispersal of cells with beneficial features such as forming new biofilms and enhancing virulence plus adhesion ( Uppuluri et al., 2010 ; Nobile and Johnson, 2015 ).…”

Section: Inhibitory Effects Of Cinnamomum On Micro...mentioning

confidence: 99%

Cinnamomum: The New Therapeutic Agents for Inhibition of Bacterial and Fungal Biofilm-Associated Infection

Didehdar

Chegini

Tabaeian

et al. 2022

Front. Cell. Infect. Microbiol.

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Due to the potent antibacterial properties of Cinnamomum and its derivatives, particularly cinnamaldehyde, recent studies have used these compounds to inhibit the growth of the most prevalent bacterial and fungal biofilms. By inhibiting flagella protein synthesis and swarming motility, Cinnamomum could suppress bacterial attachment, colonization, and biofilm formation in an early stage. Furthermore, by downregulation of Cyclic di‐guanosine monophosphate (c‐di‐GMP), biofilm-related genes, and quorum sensing, this compound suppresses intercellular adherence and accumulation of bacterial cells in biofilm and inhibits important bacterial virulence factors. In addition, Cinnamomum could lead to preformed biofilm elimination by enhancing membrane permeability and the disruption of membrane integrity. Moreover, this substance suppresses the Candida species adherence to the oral epithelial cells, leading to the cell wall deformities, damage, and leakages of intracellular material that may contribute to the established Candida’s biofilm elimination. Therefore, by inhibiting biofilm maturation and destroying the external structure of biofilm, Cinnamomum could boost antibiotic treatment success in combination therapy. However, Cinnamomum has several disadvantages, such as poor solubility in aqueous solution, instability, and volatility; thus, the use of different drug-delivery systems may resolve these limitations and should be further considered in future investigations. Overall, Cinnamomum could be a promising agent for inhibiting microbial biofilm-associated infection and could be used as a catheter and other medical materials surface coatings to suppress biofilm formation. Nonetheless, further in vitro toxicology analysis and animal experiments are required to confirm the reported molecular antibiofilm effect of Cinnamomum and its derivative components against microbial biofilm.

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“… Miranda-Cadena et al (2021b) used various natural compounds, including carvacrol and cinnamaldehyde, against the planktonic and sessile cells of Candida . The authors evaluated the reduction in the biofilm metabolic activity and biomass during the adhesion as well as mature biofilm phases.…”

Section: Carvacrolmentioning

confidence: 99%

“…The microscopic observations also showed a loss of the cell viability of Candida biofilm community after carvacrol treatment. Cinnamaldehyde showed a better function in preventing biofilm formation, while carvacrol more effectively degraded mature Candida biofilm ( Miranda-Cadena et al, 2021b ). Thus, the combined use of carvacrol and cinnamaldehyde could be a promising approach for suppressing Candida biofilm-associated infections due to its interference with various biofilm formation stages.…”

Section: Carvacrolmentioning

confidence: 99%

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

et al. 2022

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The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.

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In vitro activities of carvacrol, cinnamaldehyde and thymol against Candida biofilms

Cited by 37 publications

References 36 publications

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

Cinnamomum: The New Therapeutic Agents for Inhibition of Bacterial and Fungal Biofilm-Associated Infection

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

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