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Review

Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.

by
Tomasz M. Karpiński
1,*,
Marcin Ożarowski
2,
Agnieszka Seremak-Mrozikiewicz
3,4,5,
Hubert Wolski
3,6 and
Artur Adamczak
7
1
Department of Medical Microbiology, Poznań University of Medical Sciences, Wieniawskiego 3, 61-712 Poznań, Poland
2
Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants, National Research Institute, Wojska Polskiego 71b, 60-630 Poznań, Poland
3
Division of Perinatology and Women’s Diseases, Poznań University of Medical Sciences, Polna 33, 60-535 Poznań, Poland
4
Laboratory of Molecular Biology in Division of Perinatology and Women’s Diseases, Poznań University of Medical Sciences, Polna 33, 60-535 Poznań, Poland
5
Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, National Research Institute, Kolejowa 2, 62-064 Plewiska, Poland
6
Division of Gynecology and Obstetrics, Podhale Multidisciplinary Hospital, Szpitalna 14, 34-400 Nowy Targ, Poland
7
Department of Botany, Breeding and Agricultural Technology of Medicinal Plants, Institute of Natural Fibres and Medicinal Plants, National Research Institute, Kolejowa 2, 62-064 Plewiska, Poland
*
Author to whom correspondence should be addressed.
J. Fungi 2021, 7(5), 360; https://doi.org/10.3390/jof7050360
Submission received: 20 March 2021 / Revised: 30 April 2021 / Accepted: 1 May 2021 / Published: 5 May 2021
(This article belongs to the Special Issue Fungal Biofilms 2020)
Versions Notes

Abstract

:
Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045–0.07 mg/L), Satureja macrosiphon (0.06–8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs.

1. Introduction

The genus Candida contains about 150 species; however, most are environmental organisms. The most medically important is Candida albicans, which accounts for about 80% of infections. C. albicans causes more than 400,000 cases of bloodstream life-threatening infections annually, with a mortality rate of about 42% [1]. Candida non-albicans species that are mainly responsible for infections are C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. dubliniensis [2]. Less frequently identified are C. guilliermondii, C. lusitaniae, C. rugosa, C. orthopsilosis, C. metapsilosis, C. famata, C. inconspicua, and C. kefyr [3].
C. albicans is a member of the commensal microflora. It colonizes the oral mucosal surface of 30–50% of healthy people. The rate of carriage increases with age and in persons with dental prostheses up to 60% [4,5,6]. Opportunistic infection caused by Candida species is termed candidiasis. At least one episode of vulvovaginal candidiasis (or thrush) concerns 50 to 75% of women of childbearing age [7]. Candidiasis can also affect the oral cavity, penis, skin, nails, cornea, and other parts of the body. In immunocompromised persons, untreated candidiasis poses the risk of systemic infection and fungemia [5,8]. Candida can be an important etiological factor in the infection of chronic wounds that are difficult to treat; this is mainly related to the production of biofilm [9].
Treatment of candidiasis depends on the infection site and the patient’s condition. According to guidelines, vulvovaginal candidiasis should be treated with oral or topical fluconazole; however, regarding C. glabrata infection, topical boric acid, nystatin, or flucytosine is suggested. In oropharyngeal candidiasis, the treatment options include clotrimazole, miconazole, or nystatin, and in severe disease, fluconazole or voriconazole. In candidemia and invasive candidiasis, the drugs of choice are echinocandins (caspofungin, micafungin, anidulafungin), fluconazole, or voriconazole; in resistant strains, amphoteticin B is used. In selected cases of candidemia caused by C. krusei, voriconazole is recommended [10,11,12]. More details can be found in the Guidelines of the Infectious Diseases Society of America [12] and the European Society of Clinical Microbiology and Infectious Diseases [11]. Increasingly, Candida species are becoming resistant to drugs. Marak and Dhanashree [13] tested the resistance of 90 Candida strains isolated from different clinical samples, such as pus, urine, blood, and body fluid. Their study revealed that about 41% of C. albicans strains are resistant to fluconazole and voriconazole. Simultaneously, about 41% of C. tropicalis strains are resistant to voriconazole and about 36% of strains to fluconazole. In strains of C. krusei, about 23% are resistant to fluconazole and about 18% to voriconazole. Rudramurthy et al. [14] studied resistance in C. auris, which is considered a multiresistant pathogen. Among 74 strains obtained from patients with candidemia, over 90% of strains were resistant to fluconazole and about 73% to voriconazole. Virulence factors of Candida species include the secretion of hydrolases, the transition of yeast to hyphae, phenotypic switching, and biofilm formation [15,16]. All microorganisms in biofilm form are more resistant to antimicrobial and host factors, which leads to difficulties in eradication [17]. It has also been shown that resistance to drugs increases significantly in the case of Candida biofilm occurrence. Biofilm prevents the spread of antifungals; moreover, fluconazole is bound by the biofilm matrix [18]. The formation of a Candida biofilm during infection increases mortality, length of hospital stay, and cost of antifungal therapy [19].
Due to the above, new antifungal drugs are sought that could effectively combat not only planktonic fungi but also fungal biofilms. The natural compounds offer promise, with many acting on Candida species or biofilms in vitro [20].
The aim of this review was to present plant-derived natural compounds that have an effect against biofilms formed by Candida species.

2. Materials and Methods

In this review, publications available in PubMed and Scopus databases and through the Google search engine were taken into account. The following keywords and their combinations were used: “antifungal,” “Candida,” “anti-biofilm,” “biofilm,” “plant,” “compound,” “extract,” and “essential oil.” The principal inclusion criterion was the inhibition of biofilm formation by at least 50%. We focused on biofilm inhibition assays, in which the time of culture allowed for Candida biofilm maturation was at least 24 hours. Articles from the year 2000 to the present were taken into account. All articles published in predatory journals were rejected.

3. Results and Discussion

3.1. Plant Preparations That Display Activity against Candida Biofilms

The present review includes 60 articles in which Candida biofilm formation was inhibited by at least 50%. It has been shown that preparations from 34 plants demonstrate activity against Candida biofilms. Among them were 29 essential oils and 16 extracts. The plants from the following families dominated: Lamiaceae (6 species in 5 genera), Myrtaceae (5 species in 4 genera), Asteraceae (4 species in 4 genera), Fabaceae (4 species in 3 genera), and Apiacae (4 species in 2 genera).
Plants from the Lamiaceae family had the best antifungal activity, including Lavandula dentata (0.045–0.07 mg/L) [21], Satureja macrosiphon (0.06–8 mg/L) [22], and Ziziphora tenuior (2.5 mg/L) [23]. Artemisia judaica (2.5 mg/L) from the Asteraceae family [24], Lawsonia inermis (2.5–12.5 mg/L) from the Lythraceae family [25], and Thymus vulgaris (12.5 mg/L) from the Lamiaceae family [26] likewise exhibited good antifungal activity (Table 1). All preparations were essential oils, with the exception of Lawsonia inermis, which was an extract. Most of the plant preparations presented in Table 1 acted on biofilm formation and/or mature biofilms.
Antibiofilm activity may vary between plants in the same family. For example, in the Lamiaceae family, essential oil from Lavandula dentata acted against C. albicans biofilm at concentrations of 0.045–0.07 µL/mL [21], while essential oil from Satureja hortensis acted against the same biofilm at concentrations of 400–4800 mg/L [51]. There may also be large differences within the same species, due to various reasons. This may be influenced by, for example, different research methodologies, the use of different strains of fungi, and different chemical compositions depending on the plant variety, country, and season of harvest. A notable example of such a difference is observed with Mentha × piperita. In studies by Benzaid et al. [44], essential oil of M. piperita acted against Candida biofilm at a concentration of 10 µL/mL. However, the work of Agarwal et al. [38] showed that the same essential oil was active at 800 µL/mL.
Changes in the content of active substances were described by Gonçalves et al. [56]. They showed that in essential oil from Mentha cervina collected in August, the amount of isomenthone was 8.7% and pulegone was 75.1%. However, in essential oil collected in February, the ratio of the two compounds reversed and amounted to 77.0% for isomenthone and 12.9% for pulegone. The method of obtaining the compounds likewise had an influence on their content in the final essential oil. In a study by Ćavar et al. [57], the composition of essential oils of Calamintha glandulosa differed depending on the extraction method. The level of menthone was 3.3% using aqueous reflux extraction, 4.7% using hydrodistillation, and 8.3% using steam distillation, while the concentration of shisofuran was only 0.1% using hydrodistillation and steam distillation, while aqueous reflux yielded 9.7%.

3.2. Plant Compounds That Display Activity against Candida Biofilm

It has been shown that 69 compounds obtained from plants demonstrate activity against Candida biofilms (Table 2). Among these, the most common are monotherpenes (20), followed by sesquiterpene lactones (7) and sesquiterpenes (6). Another big group is also phenolic compounds, including phenols (6), phenolic acids (5), phenolic aldehydes (2), polyphenols (2), and phenolic alcohol (1).
In terms of activity, large differences were found, depending on the authors cited. Eugenol and thymol serve as good examples. Both compounds exhibited excellent activity in some studies (from 12.5 mg/L for eugenol [58] and 1.56 mg/L for thymol [26]), and in other studies, the activity was very poor (up to 80,000 for both [59]). These differences may be related, for example, to a different purity of the compound, a different fungal suspension density, or even to the use of other Candida strains with different sensitivities to chemical substances. A number of other factors, such as the type of culture medium, pH of the medium, incubation time, and temperature may likewise influence the antimicrobial activity [20].
According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the antifungal clinical breakpoints are between 0.001 mg/L and 16 mg/L [60]. Using EUCAST guidelines in this review, the most active compounds that inhibit (>50%) Candida biofilm formation are lichochalcone A (from 0.2 mg/L) [61], thymol (from 3.12 mg/L) [26], dioscin (from 3.9 mg/L) [31], baicalein (from 4 mg/L) [62], warburganal (4.5 mg/L) [52], pterostilbene, waltheriones and riccardin D (both from 8 mg/L) [63,64,65], polygodial (10.8 mg/L) [52], cannabidiol and eugenol (both from 12.5 mg/L) [58,66], and ivalin (15.4 mg/L) [67]. It is interesting that monotherpenes, which represent the highest percentage of substances listed in Table 2, are not the most active compounds. The two larger groups with the best activity are phenolic compounds (thymol, pterostilbene, and eugenol), and sesquiterpene derivatives (warburganal, polygodial, and ivalin). Single compounds with the highest observed activity belong to chalconoids (lichochalcone A), steroidal saponins (dioscin), flavonoids (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyls (riccardin D), and cannabinoids (cannabidiol). Most of the compounds presented in Table 2 acted on biofilm formation and/or mature biofilm.

4. Conclusions

Plant preparations (essential oils and extracts) and pure compounds exhibit anti-biofilm activity against Candida species. Some of them are characterized by high activity in concentrations below 16 mg/L. Given this activity at relatively low concentrations, some may prove to be promising alternatives to antifungal drugs, especially in the cases of resistant or multiresistant strains of Candida. Moreover, the simple chemical structures involved and relative ease of extraction from natural sources warrant further research into the development of new, promising, and much-needed plant-based antifungals.

Author Contributions

Conceptualization, T.M.K. and M.O.; methodology, T.M.K.; analysis of results, T.M.K. and M.O.; writing—original draft preparation, T.M.K., M.O., A.S.-M., H.W., and A.A.; writing—review and editing, T.M.K. and M.O.; supervision, T.M.K.; funding acquisition, T.M.K. and H.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Acknowledgments

We are very grateful to Mark Stasiewicz for English language corrections.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Brown, G.D.; Denning, D.W.; Gow, N.A.R.; Levitz, S.M.; Netea, M.G.; White, T.C. Hidden Killers: Human Fungal Infections. Sci. Transl. Med. 2012, 4, 165rv13. [Google Scholar] [CrossRef] [Green Version]
  2. Ciurea, C.N.; Kosovski, I.-B.; Mare, A.D.; Toma, F.; Pintea-Simon, I.A.; Man, A. Candida and Candidiasis-Opportunism Versus Pathogenicity: A Review of the Virulence Traits. Microorganisms 2020, 8, 857. [Google Scholar] [CrossRef] [PubMed]
  3. Moran, G.; Coleman, D.; Sullivan, D. An Introduction to the Medically Important Candida Species. In Candida and Candidiasis, 2nd ed.; Wiley: Hoboken, NJ, USA, 2012; pp. 11–25. [Google Scholar]
  4. Buranarom, N.; Komin, O.; Matangkasombut, O. Hyposalivation, Oral Health, and Candida Colonization in Independent Dentate Elders. PLoS ONE 2020, 15, e0242832. [Google Scholar] [CrossRef] [PubMed]
  5. Arya, N.R.; Naureen, R.B. Candidiasis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021. [Google Scholar]
  6. Millet, N.; Solis, N.V.; Swidergall, M. Mucosal IgA Prevents Commensal Candida Albicans Dysbiosis in the Oral Cavity. Front. Immunol. 2020, 11, 555363. [Google Scholar] [CrossRef] [PubMed]
  7. Sobel, J.D. Vulvovaginal Candidosis. Lancet 2007, 369, 1961–1971. [Google Scholar] [CrossRef]
  8. Vila, T.; Sultan, A.S.; Montelongo-Jauregui, D.; Jabra-Rizk, M.A. Oral Candidiasis: A Disease of Opportunity. J. Fungi 2020, 6, 15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  9. Karpiński, T.; Sopata, M.; Mańkowski, B. The Antimicrobial Effectiveness of Antiseptics as a Challenge in Hard to Heal Wounds. Leczenie Ran 2020, 17, 88–94. [Google Scholar] [CrossRef]
  10. Bhattacharya, S.; Sae-Tia, S.; Fries, B.C. Candidiasis and Mechanisms of Antifungal Resistance. Antibiotics 2020, 9, 312. [Google Scholar] [CrossRef]
  11. Cornely, O.A.; Bassetti, M.; Calandra, T.; Garbino, J.; Kullberg, B.J.; Lortholary, O.; Meersseman, W.; Akova, M.; Arendrup, M.C.; Arikan-Akdagli, S.; et al. ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Non-Neutropenic Adult Patients. Clin. Microbiol. Infect. 2012, 18 (Suppl. 7), 19–37. [Google Scholar] [CrossRef] [Green Version]
  12. Pappas, P.G.; Kauffman, C.A.; Andes, D.R.; Clancy, C.J.; Marr, K.A.; Ostrosky-Zeichner, L.; Reboli, A.C.; Schuster, M.G.; Vazquez, J.A.; Walsh, T.J.; et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016, 62, e1–e50. [Google Scholar] [CrossRef]
  13. Marak, M.B.; Dhanashree, B. Antifungal Susceptibility and Biofilm Production of Candida Spp. Isolated from Clinical Samples. Int. J. Microbiol. 2018, 2018, 7495218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Rudramurthy, S.M.; Chakrabarti, A.; Paul, R.A.; Sood, P.; Kaur, H.; Capoor, M.R.; Kindo, A.J.; Marak, R.S.K.; Arora, A.; Sardana, R.; et al. Candida auris Candidaemia in Indian ICUs: Analysis of Risk Factors. J. Antimicrob. Chemother. 2017, 72, 1794–1801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Mayer, F.L.; Wilson, D.; Hube, B. Candida Albicans Pathogenicity Mechanisms. Virulence 2013, 4, 119–128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Łaska, G.; Sienkiewicz, A. Antifungal Activity of the Rhizome Extracts of Pulsatilla Vulgaris against Candida Glabrata. Eur. J. Biol. Res. 2019, 9, 93–103. [Google Scholar]
  17. Gebreyohannes, G.; Nyerere, A.; Bii, C.; Sbhatu, D.B. Challenges of Intervention, Treatment, and Antibiotic Resistance of Biofilm-Forming Microorganisms. Heliyon 2019, 5, e02192. [Google Scholar] [CrossRef] [Green Version]
  18. Pereira, R.; Dos Santos Fontenelle, R.O.; de Brito, E.H.S.; de Morais, S.M. Biofilm of Candida Albicans: Formation, Regulation and Resistance. J. Appl. Microbiol. 2020. [Google Scholar] [CrossRef] [PubMed]
  19. Tumbarello, M.; Fiori, B.; Trecarichi, E.M.; Posteraro, P.; Losito, A.R.; De Luca, A.; Sanguinetti, M.; Fadda, G.; Cauda, R.; Posteraro, B. Risk Factors and Outcomes of Candidemia Caused by Biofilm-Forming Isolates in a Tertiary Care Hospital. PLoS ONE 2012, 7, e33705. [Google Scholar] [CrossRef] [Green Version]
  20. Karpiński, T.M. Essential Oils of Lamiaceae Family Plants as Antifungals. Biomolecules 2020, 10, 103. [Google Scholar] [CrossRef] [Green Version]
  21. Müller-Sepúlveda, A.; Chevecich, C.C.; Jara, J.A.; Belmar, C.; Sandoval, P.; Meyer, R.S.; Quijada, R.; Moura, S.; López-Muñoz, R.; Díaz-Dosque, M.; et al. Chemical Characterization of Lavandula Dentata Essential Oil Cultivated in Chile and Its Antibiofilm Effect against Candida Albicans. Planta Med. 2020, 86, 1225–1234. [Google Scholar] [CrossRef]
  22. Motamedi, M.; Saharkhiz, M.J.; Pakshir, K.; Amini Akbarabadi, S.; Alikhani Khordshami, M.; Asadian, F.; Zareshahrabadi, Z.; Zomorodian, K. Chemical Compositions and Antifungal Activities of Satureja Macrosiphon against Candida and Aspergillus Species. Curr. Med. Mycol. 2019, 5, 20–25. [Google Scholar] [CrossRef]
  23. Abu-Darwish, M.S.; Cabral, C.; Gonçalves, M.J.; Cavaleiro, C.; Cruz, M.T.; Paoli, M.; Tomi, F.; Efferth, T.; Salgueiro, L. Ziziphora Tenuior, L. Essential Oil from Dana Biosphere Reserve (Southern Jordan); Chemical Characterization and Assessment of Biological Activities. J. Ethnopharmacol. 2016, 194, 963–970. [Google Scholar] [CrossRef] [PubMed]
  24. Abu-Darwish, M.S.; Cabral, C.; Gonçalves, M.J.; Cavaleiro, C.; Cruz, M.T.; Zulfiqar, A.; Khan, I.A.; Efferth, T.; Salgueiro, L. Chemical Composition and Biological Activities of Artemisia Judaica Essential Oil from Southern Desert of Jordan. J. Ethnopharmacol. 2016, 191, 161–168. [Google Scholar] [CrossRef]
  25. Soliman, S.S.M.; Semreen, M.H.; El-Keblawy, A.A.; Abdullah, A.; Uppuluri, P.; Ibrahim, A.S. Assessment of Herbal Drugs for Promising Anti-Candida Activity. BMC Complement. Altern. Med. 2017, 17, 257. [Google Scholar] [CrossRef] [Green Version]
  26. Jafri, H.; Ahmad, I. Thymus Vulgaris Essential Oil and Thymol Inhibit Biofilms and Interact Synergistically with Antifungal Drugs against Drug Resistant Strains of Candida Albicans and Candida Tropicalis. J. Mycol. Med. 2020, 30, 100911. [Google Scholar] [CrossRef] [PubMed]
  27. Wang, Z.-J.; Zhu, Y.-Y.; Yi, X.; Zhou, Z.-S.; He, Y.-J.; Zhou, Y.; Qi, Z.-H.; Jin, D.-N.; Zhao, L.-X.; Luo, X.-D. Bioguided Isolation, Identification and Activity Evaluation of Antifungal Compounds from Acorus Tatarinowii Schott. J. Ethnopharmacol. 2020, 261, 113119. [Google Scholar] [CrossRef]
  28. Said, M.M.; Watson, C.; Grando, D. Garlic Alters the Expression of Putative Virulence Factor Genes SIR2 and ECE1 in Vulvovaginal C. Albicans Isolates. Sci. Rep. 2020, 10, 3615. [Google Scholar] [CrossRef] [Green Version]
  29. Bersan, S.M.F.; Galvão, L.C.C.; Goes, V.F.F.; Sartoratto, A.; Figueira, G.M.; Rehder, V.L.G.; Alencar, S.M.; Duarte, R.M.T.; Rosalen, P.L.; Duarte, M.C.T. Action of Essential Oils from Brazilian Native and Exotic Medicinal Species on Oral Biofilms. BMC Complement. Altern. Med. 2014, 14, 451. [Google Scholar] [CrossRef] [Green Version]
  30. Teodoro, G.R.; Gontijo, A.V.L.; Salvador, M.J.; Tanaka, M.H.; Brighenti, F.L.; Delbem, A.C.B.; Delbem, Á.C.B.; Koga-Ito, C.Y. Effects of Acetone Fraction From Buchenavia Tomentosa Aqueous Extract and Gallic Acid on Candida Albicans Biofilms and Virulence Factors. Front. Microbiol. 2018, 9, 647. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  31. Barros Cota, B.; Batista Carneiro de Oliveira, D.; Carla Borges, T.; Cristina Catto, A.; Valverde Serafim, C.; Rogelis Aquiles Rodrigues, A.; Kohlhoff, M.; Leomar Zani, C.; Assunção Andrade, A. Antifungal Activity of Extracts and Purified Saponins from the Rhizomes of Chamaecostus Cuspidatus against Candida and Trichophyton Species. J. Appl. Microbiol. 2021, 130, 61–75. [Google Scholar] [CrossRef] [PubMed]
  32. Wijesinghe, G.K.; Maia, F.C.; de Oliveira, T.R.; de Feiria, S.N.B.; Joia, F.; Barbosa, J.P.; Boni, G.C.; de Cássia Orlandi Sardi, J.; Rosalen, P.L.; Höfling, J.F. Effect of Cinnamomum Verum Leaf Essential Oil on Virulence Factors of Candida Species and Determination of the In-Vivo Toxicity with Galleria Mellonella Model. Mem. Inst. Oswaldo. Cruz. 2020, 115, e200349. [Google Scholar] [CrossRef]
  33. Pedroso, R.D.S.; Balbino, B.L.; Andrade, G.; Dias, M.C.P.S.; Alvarenga, T.A.; Pedroso, R.C.N.; Pimenta, L.P.; Lucarini, R.; Pauletti, P.M.; Januário, A.H.; et al. In Vitro and In Vivo Anti-Candida Spp. Activity of Plant-Derived Products. Plants 2019, 8, 494. [Google Scholar] [CrossRef] [Green Version]
  34. Andrade, G.; Orlando, H.C.S.; Scorzoni, L.; Pedroso, R.S.; Abrão, F.; Carvalho, M.T.M.; Veneziani, R.C.S.; Ambrósio, S.R.; Bastos, J.K.; Mendes-Giannini, M.J.S.; et al. Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity. J. Fungi 2020, 6, 153. [Google Scholar] [CrossRef]
  35. de Almeida Freires, I.; Murata, R.M.; Furletti, V.F.; Sartoratto, A.; de Alencar, S.M.; Figueira, G.M.; de Oliveira Rodrigues, J.A.; Duarte, M.C.T.; Rosalen, P.L. Coriandrum Sativum L. (Coriander) Essential Oil: Antifungal Activity and Mode of Action on Candida spp., and Molecular Targets Affected in Human Whole-Genome Expression. PLoS ONE 2014, 9, e99086. [Google Scholar] [CrossRef] [Green Version]
  36. Manoharan, R.K.; Lee, J.-H.; Kim, Y.-G.; Kim, S.-I.; Lee, J. Inhibitory Effects of the Essential Oils α-Longipinene and Linalool on Biofilm Formation and Hyphal Growth of Candida Albicans. Biofouling 2017, 33, 143–155. [Google Scholar] [CrossRef] [PubMed]
  37. Khan, M.S.A.; Ahmad, I. Biofilm Inhibition by Cymbopogon Citratus and Syzygium Aromaticum Essential Oils in the Strains of Candida Albicans. J. Ethnopharmacol. 2012, 140, 416–423. [Google Scholar] [CrossRef] [PubMed]
  38. Agarwal, V.; Lal, P.; Pruthi, V. Prevention of Candida Albicans Biofilm by Plant Oils. Mycopathologia 2008, 165, 13–19. [Google Scholar] [CrossRef] [PubMed]
  39. De Toledo, L.G.; Ramos, M.A.D.S.; Spósito, L.; Castilho, E.M.; Pavan, F.R.; Lopes, É.D.O.; Zocolo, G.J.; Silva, F.A.N.; Soares, T.H.; Dos Santos, A.G.; et al. Essential Oil of Cymbopogon Nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species. Int. J. Mol. Sci. 2016, 17, 1252. [Google Scholar] [CrossRef] [Green Version]
  40. Hendry, E.R.; Worthington, T.; Conway, B.R.; Lambert, P.A. Antimicrobial Efficacy of Eucalyptus Oil and 1,8-Cineole Alone and in Combination with Chlorhexidine Digluconate against Microorganisms Grown in Planktonic and Biofilm Cultures. J. Antimicrob. Chemother. 2009, 64, 1219–1225. [Google Scholar] [CrossRef]
  41. Quatrin, P.M.; Verdi, C.M.; de Souza, M.E.; de Godoi, S.N.; Klein, B.; Gundel, A.; Wagner, R.; de Almeida Vaucher, R.; Ourique, A.F.; Santos, R.C.V. Antimicrobial and Antibiofilm Activities of Nanoemulsions Containing Eucalyptus Globulus Oil against Pseudomonas Aeruginosa and Candida spp. Microb. Pathog. 2017, 112, 230–242. [Google Scholar] [CrossRef] [PubMed]
  42. Sardi, J.d.C.O.; Freires, I.A.; Lazarini, J.G.; Infante, J.; de Alencar, S.M.; Rosalen, P.L. Unexplored Endemic Fruit Species from Brazil: Antibiofilm Properties, Insights into Mode of Action, and Systemic Toxicity of Four Eugenia spp. Microb. Pathog. 2017, 105, 280–287. [Google Scholar] [CrossRef]
  43. Popović, V.; Stojković, D.; Nikolić, M.; Heyerick, A.; Petrović, S.; Soković, M.; Niketić, M. Extracts of Three Laserpitium L. Species and Their Principal Components Laserpitine and Sesquiterpene Lactones Inhibit Microbial Growth and Biofilm Formation by Oral Candida Isolates. Food. Funct. 2015, 6, 1205–1211. [Google Scholar] [CrossRef]
  44. Benzaid, C.; Belmadani, A.; Djeribi, R.; Rouabhia, M. The Effects of Mentha × Piperita Essential Oil on C. Albicans Growth, Transition, Biofilm Formation, and the Expression of Secreted Aspartyl Proteinases Genes. Antibiotics 2019, 8, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Cannas, S.; Molicotti, P.; Usai, D.; Maxia, A.; Zanetti, S. Antifungal, Anti-Biofilm and Adhesion Activity of the Essential Oil of Myrtus Communis L. against Candida Species. Nat. Prod. Res. 2014, 28, 2173–2177. [Google Scholar] [CrossRef]
  46. Stojković, D.; Dias, M.I.; Drakulić, D.; Barros, L.; Stevanović, M.; C F R Ferreira, I.; D Soković, M. Methanolic Extract of the Herb Ononis Spinosa L. Is an Antifungal Agent with No Cytotoxicity to Primary Human Cells. Pharmaceuticals 2020, 13, 78. [Google Scholar] [CrossRef] [PubMed]
  47. Souza, C.M.C.; Pereira Junior, S.A.; Moraes, T.d.S.; Damasceno, J.L.; Amorim Mendes, S.; Dias, H.J.; Stefani, R.; Tavares, D.C.; Martins, C.H.G.; Crotti, A.E.M.; et al. Antifungal Activity of Plant-Derived Essential Oils on Candida Tropicalis Planktonic and Biofilms Cells. Med. Mycol. 2016, 54, 515–523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Curvelo, J.A.R.; Marques, A.M.; Barreto, A.L.S.; Romanos, M.T.V.; Portela, M.B.; Kaplan, M.A.C.; Soares, R.M.A. A Novel Nerolidol-Rich Essential Oil from Piper Claussenianum Modulates Candida Albicans Biofilm. J. Med. Microbiol. 2014, 63, 697–702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  49. Bakkiyaraj, D.; Nandhini, J.R.; Malathy, B.; Pandian, S.K. The Anti-Biofilm Potential of Pomegranate (Punica Granatum L.) Extract against Human Bacterial and Fungal Pathogens. Biofouling 2013, 29, 929–937. [Google Scholar] [CrossRef] [PubMed]
  50. Alves-Silva, J.M.; Zuzarte, M.; Gonçalves, M.J.; Cruz, M.T.; Cavaleiro, C.; Salgueiro, L. Unveiling the Bioactive Potential of the Essential Oil of a Portuguese Endemism, Santolina Impressa. J. Ethnopharmacol. 2019, 244, 112120. [Google Scholar] [CrossRef]
  51. Sharifzadeh, A.; Khosravi, A.R.; Ahmadian, S. Chemical Composition and Antifungal Activity of Satureja Hortensis L. Essentiall Oil against Planktonic and Biofilm Growth of Candida Albicans Isolates from Buccal Lesions of HIV(+) Individuals. Microb. Pathog. 2016, 96, 1–9. [Google Scholar] [CrossRef]
  52. Kipanga, P.N.; Liu, M.; Panda, S.K.; Mai, A.H.; Veryser, C.; Van Puyvelde, L.; De Borggraeve, W.M.; Van Dijck, P.; Matasyoh, J.; Luyten, W. Biofilm Inhibiting Properties of Compounds from the Leaves of Warburgia Ugandensis Sprague Subsp. Ugandensis against Candida and Staphylococcal Biofilms. J. Ethnopharmacol. 2020, 248, 112352. [Google Scholar] [CrossRef] [PubMed]
  53. Gabriela, N.; Rosa, A.M.; Catiana, Z.I.; Soledad, C.; Mabel, O.R.; Esteban, S.J.; Veronica, B.; Daniel, W.; Ines, I.M. The Effect of Zuccagnia Punctata, an Argentine Medicinal Plant, on Virulence Factors from Candida Species. Nat. Prod. Commun. 2014, 9, 933–936. [Google Scholar] [CrossRef] [Green Version]
  54. Karpiński, T.M. Efficacy of Octenidine against Pseudomonas Aeruginosa Strains. Eur. J. Biol. Res. 2019, 9, 135–140. [Google Scholar]
  55. Loures, F.V.; Levitz, S.M. XTT Assay of Antifungal Activity. Bio. Protoc. 2015, 5, e1543. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Gonçalves, M.J.; Vicente, A.M.; Cavaleiro, C.; Salgueiro, L. Composition and Antifungal Activity of the Essential Oil of Mentha Cervina from Portugal. Nat. Prod. Res. 2007, 21, 867–871. [Google Scholar] [CrossRef] [Green Version]
  57. Ćavar, S.; Vidic, D.; Maksimović, M. Volatile Constituents, Phenolic Compounds, and Antioxidant Activity of Calamintha Glandulosa (Req.) Bentham. J. Sci. Food Agric. 2013, 93, 1758–1764. [Google Scholar] [CrossRef]
  58. Khan, M.S.A.; Ahmad, I. Antibiofilm Activity of Certain Phytocompounds and Their Synergy with Fluconazole against Candida Albicans Biofilms. J. Antimicrob. Chemother. 2012, 67, 618–621. [Google Scholar] [CrossRef] [Green Version]
  59. Pemmaraju, S.C.; Pruthi, P.A.; Prasad, R.; Pruthi, V. Candida Albicans Biofilm Inhibition by Synergistic Action of Terpenes and Fluconazole. Indian J. Exp. Biol. 2013, 51, 1032–1037. [Google Scholar]
  60. EUCAST: Breakpoints for Antifungals. Available online: https://eucast.org/astoffungi/clinicalbreakpointsforantifungals/ (accessed on 19 March 2021).
  61. Messier, C.; Grenier, D. Effect of Licorice Compounds Licochalcone A, Glabridin and Glycyrrhizic Acid on Growth and Virulence Properties of Candida Albicans. Mycoses 2011, 54, e801–e806. [Google Scholar] [CrossRef] [PubMed]
  62. Cao, Y.; Dai, B.; Wang, Y.; Huang, S.; Xu, Y.; Cao, Y.; Gao, P.; Zhu, Z.; Jiang, Y. In Vitro Activity of Baicalein against Candida Albicans Biofilms. Int. J. Antimicrob. Agents 2008, 32, 73–77. [Google Scholar] [CrossRef] [PubMed]
  63. Cretton, S.; Dorsaz, S.; Azzollini, A.; Favre-Godal, Q.; Marcourt, L.; Ebrahimi, S.N.; Voinesco, F.; Michellod, E.; Sanglard, D.; Gindro, K.; et al. Antifungal Quinoline Alkaloids from Waltheria Indica. J. Nat. Prod. 2016, 79, 300–307. [Google Scholar] [CrossRef]
  64. Cheng, A.; Sun, L.; Wu, X.; Lou, H. The Inhibitory Effect of a Macrocyclic Bisbibenzyl Riccardin D on the Biofilms of Candida Albicans. Biol. Pharm. Bull. 2009, 32, 1417–1421. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Hu, D.-D.; Zhang, R.-L.; Zou, Y.; Zhong, H.; Zhang, E.-S.; Luo, X.; Wang, Y.; Jiang, Y.-Y. The Structure-Activity Relationship of Pterostilbene Against Candida Albicans Biofilms. Molecules 2017, 22, 360. [Google Scholar] [CrossRef] [Green Version]
  66. Feldman, M.; Sionov, R.V.; Mechoulam, R.; Steinberg, D. Anti-Biofilm Activity of Cannabidiol against Candida Albicans. Microorganisms 2021, 9, 441. [Google Scholar] [CrossRef] [PubMed]
  67. Xie, C.; Sun, L.; Meng, L.; Wang, M.; Xu, J.; Bartlam, M.; Guo, Y. Sesquiterpenes from Carpesium Macrocephalum Inhibit Candida Albicans Biofilm Formation and Dimorphism. Bioorg. Med. Chem. Lett. 2015, 25, 5409–5411. [Google Scholar] [CrossRef] [PubMed]
  68. Raut, J.S.; Shinde, R.B.; Chauhan, N.M.; Karuppayil, S.M. Phenylpropanoids of Plant Origin as Inhibitors of Biofilm Formation by Candida Albicans. J. Microbiol. Biotechnol. 2014, 24, 1216–1225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  69. Raut, J.S.; Shinde, R.B.; Chauhan, N.M.; Karuppayil, S.M. Terpenoids of Plant Origin Inhibit Morphogenesis, Adhesion, and Biofilm Formation by Candida Albicans. Biofouling 2013, 29, 87–96. [Google Scholar] [CrossRef] [PubMed]
  70. Ivanov, M.; Kannan, A.; Stojković, D.S.; Glamočlija, J.; Calhelha, R.C.; Ferreira, I.C.F.R.; Sanglard, D.; Soković, M. Camphor and Eucalyptol-Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity. Int. J. Mol. Sci. 2021, 22, 483. [Google Scholar] [CrossRef] [PubMed]
  71. Dalleau, S.; Cateau, E.; Bergès, T.; Berjeaud, J.-M.; Imbert, C. In Vitro Activity of Terpenes against Candida Biofilms. Int. J. Antimicrob. Agents 2008, 31, 572–576. [Google Scholar] [CrossRef] [PubMed]
  72. Touil, H.F.Z.; Boucherit, K.; Boucherit-Otmani, Z.; Khoder, G.; Madkour, M.; Soliman, S.S.M. Optimum Inhibition of Amphotericin-B-Resistant Candida Albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids. Biomolecules 2020, 10, 342. [Google Scholar] [CrossRef] [Green Version]
  73. Janeczko, M.; Masłyk, M.; Kubiński, K.; Golczyk, H. Emodin, a Natural Inhibitor of Protein Kinase CK2, Suppresses Growth, Hyphal Development, and Biofilm Formation of Candida Albicans. Yeast 2017, 34, 253–265. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Ali, I.; Khan, F.G.; Suri, K.A.; Gupta, B.D.; Satti, N.K.; Dutt, P.; Afrin, F.; Qazi, G.N.; Khan, I.A. In Vitro Antifungal Activity of Hydroxychavicol Isolated from Piper Betle L. Ann. Clin. Microbiol. Antimicrob. 2010, 9, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Abirami, G.; Alexpandi, R.; Durgadevi, R.; Kannappan, A.; Veera Ravi, A. Inhibitory Effect of Morin Against Candida Albicans Pathogenicity and Virulence Factor Production: An in Vitro and in Vivo Approaches. Front. Microbiol. 2020, 11, 561298. [Google Scholar] [CrossRef] [PubMed]
  76. Rivas da Silva, A.C.; Lopes, P.M.; Barros de Azevedo, M.M.; Costa, D.C.M.; Alviano, C.S.; Alviano, D.S. Biological Activities of α-Pinene and β-Pinene Enantiomers. Molecules 2012, 17, 6305–6316. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Lemos, A.S.O.; Florêncio, J.R.; Pinto, N.C.C.; Campos, L.M.; Silva, T.P.; Grazul, R.M.; Pinto, P.F.; Tavares, G.D.; Scio, E.; Apolônio, A.C.M.; et al. Antifungal Activity of the Natural Coumarin Scopoletin Against Planktonic Cells and Biofilms From a Multidrug-Resistant Candida Tropicalis Strain. Front. Microbiol. 2020, 11, 1525. [Google Scholar] [CrossRef]
  78. Kim, H.-R.; Eom, Y.-B. Antifungal and Anti-Biofilm Effects of 6-Shogaol against Candida Auris. J. Appl. Microbiol. 2020. [Google Scholar] [CrossRef] [PubMed]
  79. Dal Piaz, F.; Bader, A.; Malafronte, N.; D’Ambola, M.; Petrone, A.M.; Porta, A.; Ben Hadda, T.; De Tommasi, N.; Bisio, A.; Severino, L. Phytochemistry of Compounds Isolated from the Leaf-Surface Extract of Psiadia Punctulata (DC.) Vatke Growing in Saudi Arabia. Phytochemistry 2018, 155, 191–202. [Google Scholar] [CrossRef] [PubMed]
  80. Shu, C.; Sun, L.; Zhang, W. Thymol Has Antifungal Activity against Candida Albicans during Infection and Maintains the Innate Immune Response Required for Function of the P38 MAPK Signaling Pathway in Caenorhabditis Elegans. Immunol. Res. 2016, 64, 1013–1024. [Google Scholar] [CrossRef] [PubMed]
  81. Braga, P.C.; Culici, M.; Alfieri, M.; Dal Sasso, M. Thymol Inhibits Candida Albicans Biofilm Formation and Mature Biofilm. Int. J. Antimicrob. Agents 2008, 31, 472–477. [Google Scholar] [CrossRef]
  82. Mandal, S.M.; Migliolo, L.; Franco, O.L.; Ghosh, A.K. Identification of an Antifungal Peptide from Trapa Natans Fruits with Inhibitory Effects on Candida Tropicalis Biofilm Formation. Peptides 2011, 32, 1741–1747. [Google Scholar] [CrossRef] [PubMed]
  83. Patel, M.; Srivastava, V.; Ahmad, A. Dodonaea Viscosa Var Angustifolia Derived 5,6,8-Trihydroxy-7,4’ Dimethoxy Flavone Inhibits Ergosterol Synthesis and the Production of Hyphae and Biofilm in Candida Albicans. J. Ethnopharmacol. 2020, 259, 112965. [Google Scholar] [CrossRef]
Table
Table 1. Antifungal (MICs) and anti-biofilm (inhibition >50%) activity of plant preparations (essential oils or extracts).
Table 1. Antifungal (MICs) and anti-biofilm (inhibition >50%) activity of plant preparations (essential oils or extracts).
Name of Plant
(Family)		Main Compounds Presented in the Reference
(EO: Essential Oil)		Targeted Species of CandidaMICs
(mg/L; mL/L)		Inhibition of Biofilm Formation by at Least 50% (mg/L; mL/L)Inhibited Stage of Biofilm; Method of Biofilm DetectionRef.
Acorus calamus var. angustatus Besser = A. tatarinowii Schott
(Acoraceae)		EO: asaraldehyde, 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol, α-asarone, β-asarone, γ-asarone,
acotatarone C		C. albicans51.250–200Mature biofilm; crystal violet and fluorescence microscopy[27]
Allium sativum L.
(Amaryllidaceae)		Extract: allicinC. albicans40060Biofilm formation; XTT[28]
Aloysia gratissima (Aff & Hook).Tr
(Verbenaceae)		EO: E-pinocamphone (16.07%), β-pinene (12.01%), guaiol (8.53%), E-pinocarveol acetate (8.19%)C. albicans15500Biofilm formation; crystal violet[29]
Artemisia judaica L.
(Asteraceae)		EO: piperitone (30.4%), camphor (16.1%), ethyl cinnamate (11.0%), chrysanthenone (6.7%)C. albicans1.252.5Mature biofilm; XTT[24]
C. guillermondii1.252.5
C. krusei1.252.5
C. parapsilosis1.252.5
C. tropicalis1.252.5
Buchenavia tomentosa Eichler
(Combretaceae)		Extract: gallic acid, kaempferol, epicatechin, ellagic acid, vitexin, and corilaginC. albicans625312.5Biofilm formation and mature biofilm; culture[30]
Chamaecostus cuspidatus (Nees & Mart.) C.Specht & D.W.Stev.
(Costaceae)		Extract: dioscin,
aferoside A, aferoside C		C. albicans25015.62Biofilm formation and mature biofilm; MTT[31]
Cinnamomum verum J. Presl
(Lauraceae)		EO: eugenol (77.22%), benzyl benzoate (4.53%), trans-caryophyllene (3.39%), acetyl eugenol (2.75%), linalool 2.11%C. albicans1000150Biofilm adhesion; XTT[32]
C. dubliniensis1000200
C. tropicalis1000350
Citrus limon (L.) Osbeck
(Rutaceae)		EO: limonene (53.4%), neral (11%), geraniol (9%), trans-limonene oxide (7%), nerol (6%)C. albicans5002000Biofilm formation and mature biofilm; XTT[33]
C. glabrata2501000
C. krusei500125
C. orthopsilosis5001000
C. parapsilosis5002000
C. tropicalis2502000
Copaifera paupera (Herzog) Dwyer
(Fabaceae)		Extract: galloylquinic acids, quercetrin, afzelinC. glabrata5.8946.87Biofilm formation and mature biofilm; XTT[34]
Copaifera reticulata Ducke
(Fabaceae)		Extract: galloylquinic acids, quercetrin, afzelinC. glabrata5.8946.87Biofilm formation and mature biofilm; XTT[34]
Coriandrum sativum L.
(Apiaceae)		EO: 1-decanol (33.91%), E-2-decen-1-ol (23.59%), 2-dodecen-1-ol (13.06%), E-2-tetradecen-1-ol (5.46%)C. albicans7250Biofilm formation; crystal violet[29]
EO: decanal (19.09%), trans-2-decenal (17.54%), 2-decen-1-ol (12.33%), cyclodecane (12.15%)C. albicans15.662.5–125Biofilm adhesion; crystal violet[35]
C. dubliniensis31.262.5–125
C. rugosa15.662.5
C. tropicalis31.231.25–250
Croton eluteria (L.) W.Wright
(Euphorbiaceae)		EO: α-pinene (29.37%), β-pinene (19.35%), camphene (10.31%), 1,8-cineole (9.68%)C. albicans40005–500Biofilm formation; confocal laser microscopy[36]
Cupressus sempervirens L.
(Cupressaceae)		EO: sabinene (20.3%), citral (20%), terpinene-4-ol (15.4%), α-pinene (8%)C. albicans2501000Biofilm formation and mature biofilm; XTT[33]
C. glabrata31.25250
C. krusei62.562.5
C. orthopsilosis31.25125
C. parapsilosis62.5500
C. tropicalis250500
Cymbopogon citratus (DC.) Stapf
(Poaceae)		EO: no compositionC. albicans180–36022.5–180Biofilm formation; XTT[37]
Cymbopogon martini (Roxb.) W.Watson
(Poaceae)		EO: no compositionC. albicans16,800800Biofilm formation; XTT[38]
Cymbopogon nardus (L.) Rendle
(Poaceae)		EO: citronellal (27.87%),
geraniol (22.77%), geranial (14.54%), citronellol (11.85%), neral (11.21%)		C. albicans10002500–5000Biofilm adhesion; XTT[39]
C. krusei250–5002500
C. parapsilosis500–10005000–10,000
Cyperus articulatus L.
(Cyperaceae)		EO: α-pinene (5.72%), mustakone (5.66%), α-bulnesene (5.02%), α-copaene (4.97%)C. albicans125250Biofilm formation; crystal violet[29]
Eucalyptus sp.
(Myrtaceae)		EO: no compositionC. albicans88Mature biofilm; luminescence[40]
Eucalyptus globulus Labill.
(Myrtaceae)		EO: 1,8-cineole (75.8%), p-cymene (7.5%), α-pinene (7.4%), limonene (6.4%)C. albicans21911,250–22,500Mature biofilm; atomic force microscopy[41]
C. glabrata21911,250–22,500
C. tropicalis88511,250–22,500
EO: no compositionC. albicans8400500Biofilm formation; XTT[38]
Eugenia brasiliensis Lam. (Myrtaceae)Extract: no compositionC. albicans15.62–31.25156Mature biofilm; scanning electron microscopy[42]
Eugenia leitonii Legrand nom. inval.
(Myrtaceae)		Extract: no compositionC. albicans15.62–250156Mature biofilm; scanning electron microscopy[42]
Helichrysum italicum (Roth) G.Don
(Asteraceae)		EO: α-pinene (27.64%), γ-elemene (23.84%), β-caryophyllene (13.05%), α-longipinene (11.25%)C. albicans600010–500Biofilm formation; confocal laser microscopy[36]
Laserpitium latifolium L.
(Apiaceae)		Extract: laserpitineC. albicans12506300Mature biofilm; luminescence[43]
C. krusei12506300
Laserpitium ochridanum Micevski
(Apiaceae)		Extract: isomontanolide,
montanolide, tarolide		C. albicans500010,000Mature biofilm; luminescence[43]
C. krusei500010,000
Laserpitium zernyi Hayek = L. siler subsp. zernyi (Hayek) Tutin
(Apiaceae)		Extract: isomontanolide,
montanolide, tarolide		C. albicans750015,000Mature biofilm; luminescence[43]
C. krusei750037,500
Lavandula dentata L.
(Lamiaceae)		EO: eucalyptol (42.66%), β-pinene (8.59%), trans-α-bisabolene (6.34%), pinocarveol (6.3%)C. albicans0.15–0.180.045–0.07Mature biofilm; XTT[21]
Lawsonia inermis L.
(Lythraceae)		Extract: no compositionC. albicans102.5–12.5Mature biofilm; MTT[25]
Lippia sidoides Cham.
(Verbenaceae)		EO: thymol (65.76%), p-cymene (17.28%), α-caryophyllene (10.46%), cyclohexanone (6.5%)C. albicans250500Biofilm formation; crystal violet[29]
Litsea cubeba (Lour.) Pers.
(Lauraceae)		EO: limonene (37%), neral (31.4%), citral (12%), linalool (4%)C. albicans5002000Biofilm formation and mature biofilm; XTT[33]
C. glabrata2502000
C. krusei62.5250
C. orthopsilosis2502000
C. parapsilosis5001000
C. tropicalis10002000
Mentha × piperita L.
(Lamiaceae)		EO: menthol (32.93%), menthone (24.41%), 1,8-cineole (7.89%)C. albicans1–1010Biofilm formation; MTT[44]
EO: no compositionC. albicans11,600800Biofilm formation; XTT[38]
Mikania glomerata Spreng
(Asteraceae)		EO: germacrene D (38.29%), α-caryophyllene (9.49%), bicyclogermacrene (7.98%), caryophyllene oxide (4.28%)C. albicans250500Biofilm formation; crystal violet[29]
Myrtus communis L.
(Myrtaceae)		EO: α-pinene (39.8%), 1,8-cineole (24.8%), limonene (10.7%), linalool (6.4%)C. albicans1250–10,000None or 1250No data; no data[45]
C. parapsilosis1250 to >16,0001250
C. tropicalis1250–16,0001250
Ononis spinosa L.
(Fabaceae)		Extract: kaempherol-O-dihexoside, kaempherol-O-hexoside-pentoside, kaempherol-O-hexoside, quercetin-O-hexoside-pentoside, acetylquercetin-O-hexosideC. albicans62010,000Mature biofilm; luminescence[46]
C. krusei6205000
C. tropicalis31010,000
Pelargonium graveolens L’Hér.
(Geraniaceae)		EO: geraniol (42.3%), linalool (20.1%), citronellol (11.1%), menthone (8.0%)C. albicans1254000–8000Mature biofilm; XTT[47]
Piper claussenianum (Miq.) C. DC.
(Piperaceae)		EO: nerolidolsC. albicans4100–96002400–12,600Mature biofilm; MTT[48]
Portulaca oleracea L.
(Portulacaceae)		Extract: no compositionC. albicans1012.5Mature biofilm; MTT[25]
Punica granatum L.
(Lythraceae)		Extract: ellagic acidC. albicans1000100–750Biofilm formation and mature biofilm; crystal violet[49]
Santolina impressa Hoffmanns. & Link
(Asteraceae)		EO: β-pinene (22.5%), 1,8-cineole (10.0%), limonene (9.1%), camphor (8.1%), β-phellandrene (8.0%)C. albicans54070–1050Biofilm formation; XTT[50]
Satureja hortensis L.
(Lamiaceae)		EO: thymol (45.9%),
gamma-terpinen (16.71%), carvacrol (12.81%), p-cymene (9.61%)		C. albicans200–400400–4800Biofilm adhesion, formation, and mature biofilm; MTT[51]
Satureja macrosiphon (Coss.) = Micromeria macrosiphon Coss.
(Lamiaceae)		EO: linalool (28.46%), borneol (16.22%), terpinene-4-ol (14.58%), cis-sabinene hydrate (12.96%)C. albicans0.06–40.06–8Biofilm formation; XTT[22]
C. dubliniensis0.25–42–8
Syzygium aromaticum (L.) Merr. & L.M.Perry = Eugenia caryophyllus (Spreng.) Bullock & S.G.Harrison
(Myrtaceae)		EO: no compositionC. albicans100–20050Biofilm formation; XTT[37]
EO: no compositionC. albicans48,0003300Biofilm formation; XTT[38]
Thymus vulgaris L.
(Lamiaceae)		EO: thymol (54.73%), carvacrol (12.42%), terpineol (4.00%), nerol acetate (2.86%), fenchol (0.5%)C. albicans1.56–2512.5Biofilm formation; absorbance, crystal violet, and scanning electron microscopy[26]
C. tropicalis25–5012.5
Warburgia ugandensis Sprague
(Canellaceae)		Extract: ugandenial A, warburganal, polygodial, alpha-linolenic acid ALAC. albicansLack of data1000Biofilm formation and mature biofilm; XTT and confocal laser microscopy[52]
C. glabrataLack of data1000
Ziziphora tenuior L.
(Lamiaceae)		EO: pulegone (46.8%),
p-menth-3-en-8-ol (12.5%),
isomenthone (6.6%),
8-hydroxymenthone (6.2%),
isomenthol (4.7%)		C. albicans1.252.5Mature biofilm; XTT[23]
Zuccagnia punctata L.
(Fabaceae)		Extract: no compositionC. albicans400100Biofilm formation and mature biofilm; XTT and crystal violet[53]
Legend: MIC—minimal inhibitory concentration; XTT—reduction assay of 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide; MTT—reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [54,55].
Table
Table 2. Antifungal and antibiofilm activity of plant compounds.
Table 2. Antifungal and antibiofilm activity of plant compounds.
Active CompoundExample of Plant OriginTargeted FungusMICs
(mg/L, mL/L)		Inhibition of Biofilm Formation by at Least 50% (mg/L, mL/L)Inhibited Stage of Biofilm; Method of Biofilm DetectionRef.
Antidesmone
(alkaloid)		Waltheria indica,
W. brachypetala		C. albicans3216Mature biofilm; XTT[63]
C. glabrata>3216
C. krusei1616
C. parapsilosis416
C. tropicalis>3216
Anisaldehyde
(phenolic aldehyde)		 Pimpinella anisum ,
Foeniculum vulgare 		C. albicans500500Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Anisic acid
(phenolic acid)		 Pimpinella anisum C. albicans40004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Anisyl alcohol
(phenolic alcohol)		 Pimpinella anisum C. albicans31500Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Baicalein
(flavonoid)		Scutellaria baicalensis,
S. lateriflora		C. albicansNo data4–32Biofilm formation; XTT[62]
Camphene
(monotherpene)		Croton eluteria,
Cinnamomum verum		C. albicansNo data500Biofilm formation; confocal laser microscopy[36]
C. albicans10002000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Camphor
(bicyclic monotherpene)		Cinnamomum camphora,
Artemisia annua		C. albicans125–250Not or 62.5–250Biofilm formation; crystal violet and absorbance[70]
C. glabrata175Not
C. krusei350Not
C. parapsilosis125Not
C. tropicalis175175
Cannabidiol
(cannabinoid)		Cannabis sativaC. albicansNo data12.5–100Biofilm formation; confocal microscopy[66]
Carvacrol
(phenol)		Thymus serpyllum,
Carum carvi,
Origanum vulgare		C. albicans250500Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
100–20,000300–1250Mature biofilm; XTT[71]
1000750–1500Biofilm formation; MTT[72]
C. glabrata100–20,000300–1250Mature biofilm; XTT[71]
C. parapsilosis100–20,000300–1250
Carvene/Limonene
(monotherpene)		Citrus × aurantium,
Citrus limon		C. albicans10004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Carvone/Carvol
(monotherpene)		Carum carvi,
Mentha spicata		C. albicans>4000250Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
β-Caryophyllene
(sesquiterpene)		Helichrysum italicum,
Caryophyllusaromaticus		C. albicansNo data100–500Biofilm formation; confocal laser microscopy[36]
1,4-Cineole
(monotherpene)		 Rosmarinus officinalis ,
Thymus vulgaris		C. albicans>40004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
1,8-Cineole/Eucalyptol
(monotherpene)		Eucalyptus globulus,
Salvia officinalis,
Pinus sylvestris		C. albicans40004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
84Mature biofilm; luminescence[40]
3000–23,000Not or 3000–23,000Biofilm formation; crystal violet and absorbance[70]
C. glabrata2000Not
C. krusei40002000–4000
C. parapsilosis20001000–2000
C. tropicalis40002000–4000
Cinnamaldehyde
(aldehyde)		Cinnamomum sp.,
Apium graveolens		C. albicans62125Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
50–40025–200Mature biofilm; XTT[58]
Cinnamic acid
(phenolic acid)		 Cinnamomum sp. C. albicans20004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Citral
(monotherpene)		Melissa officinalis,
Backhousia citriodora		C. albicans5001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Citronellal
(monotherpene)		 Cymbopogon citratus ,
Melissa officinalis		C. albicans5001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
β-Citronellol
(monotherpene)		Melissa officinalis,
Pelargonium roseum		C. albicans5001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Cuminaldehyde
(monotherpene)		 Carum carvi ,
Cinnamomum verum 		C. albicans1000 to >40006000–7000Biofilm formation; MTT[72]
p-Cymene
(monotherpene)		Thymus vulgaris,
Eucalyptus sp.		C. albicans20004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
8-Deoxoantidesmone
(alkaloid)		Waltheria indicaC. albicans1632Mature biofilm; XTT[63]
C. glabrata>3232
C. krusei3232
C. parapsilosis3232
C. tropicalis>3232
2′,4′-Dihydroxy-3′-methoxychalcone
(chalcone)		Zuccagnia punctata,
Oxytropis falcata		C. albicans10025Biofilm formation and mature biofilm; XTT and crystal violet[53]
Dioscin
(steroidal saponin)		Dioscorea sp.,
Chamaecostus		C. albicans3.9–15.623.9–31.25Biofilm formation and mature biofilm; MTT[31]
Ellagic acid
(polyphenol)		Punica granatum L.C. albicans75–10025–40Biofilm formation and mature biofilm; crystal violet[49]
Emodin
(anthraquinone)		Rheum palmatum,
Frangula alnus		C. albicans12.5–50Not or 100–400Biofilm adhesion; MTT[73]
4α,5α-Epoxy-10α,14H-1-epi-inuviscolide
(sesquiterpene lactone)		Carpesium macrocephalumC. albicans>12838Biofilm formation and mature biofilm; XTT[67]
Eugenol
(phenol)		 Syzygium aromaticum ,
Cinnamomum sp. 		C. albicans50–40012.5–200Mature biofilm; XTT[58]
250500Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
500500Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
120010,000–80,000Mature biofilm; XTT[59]
Farnesol
(sesquiterpene)		Tilia sp.,
Cymbopogon sp.		C. albicans1000500Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
1000500Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Gallic acid
(phenolic acid)		Polygonum sp.,
Buchenavia tomentosa		C. albicans50002500Biofilm formation and mature biofilm; culture[30]
Geraniol
(monotherpene)		Pelargonium graveolens,
Rosa sp.		C. albicans10001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
C. albicans100–20,000300–1250Mature biofilm; XTT[71]
C. albicansNo data1000–8000Mature biofilm; XTT[47]
C. glabrata100–20,000300–1250Mature biofilm; XTT[71]
C. parapsilosis100–20,000300–1250
Guaiacol
(phenol)		 Guaiacum officinale ,
Apium graveolens		C. albicans5001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Hydroxychavicol
(phenol)		Piper betleC. albicans125–500125–1000Biofilm formation and mature biofilm; XTT[74]
β-Ionone
(carotenoid)		 Lawsonia inermis ,
Camellia sinensis 		C. albicans250250Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Isomontanolide
(sesquiterpenic lactone)		Laserpitium ochridanum,
L. zernyi		C. albicans50250Mature biofilm; luminescence[43]
C. krusei200250
Isopulegol
(monotherpene)		 Mentha rotundifolia,
Melissa officinalis		C. albicans>4000250Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Ivalin
(sesquiterpene lactone)		Geigeria aspera,
Carpesium macrocephalum		C. albicans>12815.4Biofilm formation and mature biofilm; XTT[67]
Laserpitine
(sesquiterpene lactone)		Laserpitium latifolium,
Laserpitiumhalleri		C. albicans200400Mature biofilm; luminescence[43]
C. krusei200400
Lichochalcone A
(chalconoid)		Glycyrrhiza sp.C. albicans6.25–12.50.2–20Biofilm formation; crystal violet[61]
Linalool
(monotherpene)		Lavandula officinalis,
Pelargonium graveolens		C. albicansNo data100–500Biofilm formation; confocal laser microscopy[36]
20001000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
No data1000–8000Mature biofilm; XTT[47]
α-Longipinene
(sesquiterpene)		Croton eluteria,
Helichrysum italicum		C. albicansNo data100–500Biofilm formation; confocal laser microscopy[36]
Menthol
(monotherpene)		Mentha spp.C. albicans>40002000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
250010,000–80,000Mature biofilm; XTT[59]
Montanolide
(sesquiterpene lactone)		Laserpitium ochridanum,
L. zernyi		C. albicans200400Mature biofilm; luminescence[43]
C. krusei200400
Morin
(flavonoid)		 Prunus dulcis ,
Morus alba 		C. albicans15037.5–600Biofilm formation; crystal violet[75]
Myrcene
(monotherpene)		Humulus lupulus,
Cannabis sativa		C. albicans10002000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Nerol
(monotherpene)		Citrus × aurantium,
Humulus lupulus		C. albicans2000500Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Nerolidols
(sesquiterpene)		Citrus × aurantium,
Piper claussenianum		C. albicans18,600–62,5002500–10,000Mature biofilm; MTT[48]
α-Pinene
(monotherpene)		Pinus sylvestris,
Picea abies		C. albicans31253125Biofilm formation; XTT[76]
β-Pinene
(monotherpene)		Pinus sylvestris,
Picea abies		C. albicans20004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
187187Biofilm formation; XTT[76]
Polygodial
(sesquiterpene)		Warburgia ugandensis, Polygonum hydropiperC. albicans4.110.8Biofilm formation and mature biofilm; XTT and confocal laser microscopy[52]
C. glabrata94.150.6–61.9
Pterostilbene
(polyphenol)		Pterocarpus marsupium, Pterocarpus santalinus,
Vitis vinifera		C. albicansNo data8–32Biofilm formation and mature biofilm; XTT[65]
Riccardin D
(macrocyclic bisbibenzyl)		Dumortiera hirsutaC. albicans168–64Mature biofilm; XTT[64]
Salicylaldehyde
(phenolic aldehyde)		Filipendula ulmaria,
Fagopyrum esculentum		C. albicans31125Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Salicylic acid
(phenolic acid)		Salix sp.,
Filipendula ulmaria		C. albicans40002000Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Scopoletin
(cumarin)		Mitracarpus frigidus,
Scopolia carniola		C. tropicalis5050Biofilm adhesion, formation, and mature biofilm; absorbance and digital scanning[77]
6-Shogaol
(phenylalkane)		Zingiber officinaleC. auris32–6416–64Mature biofilm; crystal violet[78]
Tarolide
(sesquiterpene lactone)		Laserpitium ochridanum,
L. zernyi		C. albicans4001000Mature biofilm; luminescence[43]
C. krusei4001000
Telekin
(sesquiterpene lactone)		Carpesium macrocephalum,
Telekia speciose		C. albicans>12836Biofilm formation and mature biofilm; XTT[67]
Terpinolene
(terpene)		Cannabis sativa,
Citrus limon		C. albicans20004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
5,7,3′,4′-Tetramethoxyflavone
(flavonoid)		Psiadia punctulate,
Kaempferia parviflora		C. albicans10040Biofilm formation; crystal violet[79]
α-Thujone
(monotherpene)		Artemisia absinthium,
Tanacetum vulgare		C. albicans>4000500Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
Thymol
(phenol)		Thymus vulgaris,
Trachyspermum copticum		C. albicans250250Mature biofilm; XTT, crystal violet, and inverted light microscopy[69]
1.56–503.12Biofilm formation; absorbance, crystal violet, and scanning electron microscopy[26]
32–128128Biofilm adhesion and mature biofilm; XTT[80]
100–20,000300–1250Mature biofilm; XTT[71]
125125–250Biofilm formation and mature biofilm; XTT[81]
12005000–80,000Mature biofilm; XTT[59]
C. tropicalis1.56–5012.5Biofilm formation; absorbance, crystal violet, and scanning electron microscopy[26]
C. glabrata100–20,000300–1250Mature biofilm; XTT[71]
C. parapsilosis100–20,000300–1250
Tn-AFP1
(protein)		Trapa natansC. tropicalis3216Mature biofilm; XTT[82]
5,6,8-Trihydroxy-7,4′
dimethoxy flavone
(flavonoid)		Thymus membranaceus subsp. membranaceus,
Dodonaea viscosa var. angustifolia 		C. albicans390390Biofilm formation and mature biofilm; MTT[83]
5(R)-Vanessine
(alkaloid)		Waltheria indicaC. albicans3216Mature biofilm; XTT[63]
C. glabrata>3216
C. krusei3216
C. parapsilosis>3216
C. tropicalis>3216
Vanillic acid
(phenolic acid)		 Angelica sinensis ,
Solanum tuberosum		C. albicans>40004000Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Vanillin
(phenol)		Vanilla planifoliaC. albicans1000500Mature biofilm; XTT, crystal violet, and inverted light microscopy[68]
Waltheriones
(alkaloid)		Waltheria indica,
W.viscosissima		C. albicans4–328–32Mature biofilm; XTT[63]
C. glabrata32 or >328–32
C. krusei16–32 or >328–32
C. parapsilosis2–32 or >328–32
C. tropicalis32 or >328–32
Warburganal
(sesquiterpene)		Warburgia sp. C. albicans44.5Biofilm formation and mature biofilm; XTT and confocal laser microscopy[52]
C. glabrata72–72.649.1–55.9
Legend: MIC—minimal inhibitory concentration; XTT—reduction assay of 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide; MTT—reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [54,55].
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Karpiński, T.M.; Ożarowski, M.; Seremak-Mrozikiewicz, A.; Wolski, H.; Adamczak, A. Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp. J. Fungi 2021, 7, 360. https://doi.org/10.3390/jof7050360

AMA Style

Karpiński TM, Ożarowski M, Seremak-Mrozikiewicz A, Wolski H, Adamczak A. Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp. Journal of Fungi. 2021; 7(5):360. https://doi.org/10.3390/jof7050360

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Karpiński, Tomasz M., Marcin Ożarowski, Agnieszka Seremak-Mrozikiewicz, Hubert Wolski, and Artur Adamczak. 2021. "Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp." Journal of Fungi 7, no. 5: 360. https://doi.org/10.3390/jof7050360

APA Style

Karpiński, T. M., Ożarowski, M., Seremak-Mrozikiewicz, A., Wolski, H., & Adamczak, A. (2021). Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp. Journal of Fungi, 7(5), 360. https://doi.org/10.3390/jof7050360

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