Tasman Medical Journal

ISSN: 2652-1881

Plant-based therapies for dermatophyte infections

Angela Mei, Bernadette Ricciardo, Edward Raby and S Prasad Kumarasinghe

ABSTRACT

Background: Resistance and side effects encountered with use of common topical and systemic antifungal drugs for dermatophyte infections highlights the need for novel therapies. Medicinal plants, which have been traditionally utilised for their antimicrobial properties to treat superficial skin infections, serve as an abundant source for the identification of new antifungal compounds.

Aim:  To summarise the current evidence for plant-based natural therapies for dermatophytic infections.

Methods: A comprehensive literature search was performed across databases PubMed, Embase and ScienceDirect using keywords ‘dermatophyte’ or ‘anti-dermatophytic’ or ‘antifungal’, combined with ‘natural, ‘ethnomedical’, ‘plant’, ‘botanical’, ‘treatment’ or ‘remedy’. Additional studies specific to the plant extract were searched using genus and species.

Results/ Discussion: Seventy plant extracts demonstrating in vitro anti-dermatophytic properties are summarised in this review. Among these, common antifungal phytochemicals found include phenolic compounds, terpenoids, terpenes, alkaloids, xanthones and glycosides including saponins. Only 21 plant extracts or their active components have been evaluated in in vivo bioassays in clinical trials and animal studies. Multiple mechanisms of action have been elucidated, including disruption to cell wall and cell membranes, inhibition of cell wall synthesis, hyphal growth, and spore germination, as well as possible in vivo anti-inflammatory and immunomodulatory effects.

Conclusion:  Based on in vitro studies, numerous plant extracts show significant therapeutic potential for the treatment of dermatophyte infections. However, more in vivo studies are required to assess the clinical effectiveness of plant extracts.

Tasman Med J 2022: 3; 21-37

Full Text

Introduction
Superficial fungal infections are estimated to affect one billion people globally each year.1 Dermatophytes are a group of keratinophilic filamentous fungi responsible for a significant proportion of fungal skin, hair and nail infections.2 These include nine genera, of which Trichophyton, Microsporum and Epidermophyton most commonly infect humans.3 The anthropophilic species T. rubrum is responsible for most infections world-wide. However, significant geographic and demographic variation exists, with a recent emerging predominance of zoophilic species M. canis and T. mentagrophytes,4 in some areas likely due to increased contact between animals and humans.  Additionally, there has been unprecedented growth of dermatophytoses in developing countries, including increases in chronic and relapsing cases associated with significant morbidity, financial burden and impaired quality of life.5

Concern has been raised regarding the development of dermatophyte resistance to existing antifungal agents, including azoles and allylamines, contributing to therapeutic failure.  Although already a major public health threat in endemic areas such as India, reports of dermatophyte resistance to terbinafine have increased globally in recent years including in Japan, European countries, Iran, Mexico and the US.6-11 Whilst previously limited to T. rubrum, resistance is now being reported in T. mentagrophytes and T. interdigitale.12Mechanisms for terbinafine and azole resistance include alteration of drug targets, drug efflux and biofilm formation.6,13 Selective pressure for resistant dermatophyte strains is multi-factorial, and may be due to poor compliance, sub-inhibitory doses, widespread self-treatment and steroid misuse.14  Moreover, cellular drug targets are limited and overlapping, for instance, allylamines, azoles, morpholines and thiocarbamates all inhibit ergosterol biosynthesis, albeit through different enzyme targets.14  This has stimulated the search for new formulations to enhance current drug effectiveness, or the development of novel antifungal compounds.15

Plants possess natural defence systems against external microbial pathogens, and serve as a limitless source of antimicrobial compounds.16 Several plants have been utilised historically by native populations to treat fungal infections, particularly in Latin America, Asia and Africa. For example, a survey conducted among 34 Ayurvedic practitioners in Sri Lanka identified 165 plants used for skin diseases, including neem (Azadirachta indica A.Juss.) and turmeric (Curcuma longa L.).17 Many of these species have been scientifically investigated in vitro, and are often chosen based on their uses in traditional medicine.

The aim of this review is to summarise the current scientific evidence in vitro and in vivo for plant based natural therapies for dermatophyte infections.

Methods
A comprehensive search of the literature was conducted across databases PubMed, Embase, and ScienceDirect from their inception to January 2021.  Keywords included ‘dermatophyte’ or ‘anti-dermatophytic’ or ‘antifungal’, combined with ‘natural’, ‘ethnomedical’, ‘plant’, ‘botanical’, ‘treatment’ or ‘remedy’.  A comprehensive list of plants was extracted from the initial search, and databases searched again using each individual plant name and ‘dermatophyte’, to identify all relevant studies.  In vitro studies included described methods of plant extraction and anti-microbial susceptibility testing methods.  Minimum inhibitory concentration (MIC) and phytochemical composition was reported if investigated within the in vitro studies selected.  In vivo studies included both animal models and clinical trials.  One hundred and ten studies of 70 plant extracts were selected after the exclusion of duplicates and irrelevant articles by AM. Concentrations of compounds are reported here using the same units as in the cited study.

Results 1:  Plants with in vitro anti-dermatophytic activity
Seventy plants demonstrated in vitro anti-dermatophytic activity (Appendix 1: click HERE). Interpretation of MIC values is difficult due to variations in methodology and no standardised minimum breakpoint concentration deemed to indicate effectiveness against dermatophytes.  Additionally, comparison between studies of the same plant extract frequently reveals discrepancies of reported MIC or diameter inhibition zone values.  Of the 70 plant extracts included in this review, 25 had more than two dedicated in vitro studies, but very few revealed consistent data.  Variations in methodology include inoculum size and preparation, incubation duration and time, criterion used for MIC determination, differences in solubility of phytochemicals in solvents used, environmental growth conditions affecting compound composition, and fungal sensitivity, all of which all significantly influence outcomes.  The use of negative and positive controls would be helpful in determining usefulness in clinical application, but these are not always applied.  Of thirty-six plant families, Lamiaceae (mints) and Myrtaceae (Myrtle) comprised the most, (10 and 8 plants respectively).  Notable plants with the highest antifungal activity as demon-strated by an MIC of < 50 μg ml-1 were Azadirachta indica A. Juss, Piper betle L., Vitis vinifera L., Terminalia chebula Retz., Lawsonia inermis L., Ocimum sanctum L., Libidibia ferrea (Mart. Ex Tul.) L.P. Queiroz, Mimosa tenuiflora (Willd.) Poir, Foeniculum vulgare Mill, Anagallis arvensis L.and Piper regnellii (Mia.) C. DC.  Across studies of plants with the lowest MIC values, many common constituents are identified. For instance, essential oil of P. betle comprising primarily eugenolreported an MIC of 0.2 – 0.4 μgml-1 against Trichophyton and Microsporum species.18 Eugenol was also the main component of O. sanctum (MIC 0.4 – 0.8 μg ml-1)18 and Syzygium aromaticum L.(MIC 160 μg ml-1)19.  Several other studies showed a weak to moderate inhibitory effect, with MICs ranging up to 160 mg ml-1 reported as having antifungal activity.  The impact of methodological variations is highlighted by a 2004 study of T. chebula aqueous extracts, which yielded an MIC against T. mentagrophytes of 600 μg ml-1, whereas a 2013 study using lyophilised ethanolic extract yielded an MIC of 3.125 μg ml-1.20

In general, plant extracts were less effective in vitro than commercial antifungal drugs.  However, isolated phytochemicals showed greater inhibitory growth effects than that of the plant extract alone, and sometimes had efficacy comparable or greater than their positive controls.  For example, macrocarpal C isolated from Eucalyptus globulus Labill.had an MIC of 1.95 μg ml-1, similar to terbinafine (0.625 µg ml-1 ) and nystatin (1.25 µg ml-1).21  Isolated thymoquinone from black cumin (Nigella sativa L.) had an MIC of 0.125 – 0.25 mg ml-1 compared to the plain ether extract (40 mg ml-1).22  Other examples include terpinen-4-ol from tea tree oil (Melaleuca alternifolia (Maiden & Betche) Cheel), limonene and methyleugenol from Thapsia villosa L., and thymol from Thymus pulegioides L.23,24,25

Synergistic activity is seen when plant extracts are used in combination with existing antifungal drugs.  In a study by Khan and Ahmad (2011), the addition of cinnamaldehyde to fluconazole reduced the MIC 8-fold against T. rubrum from 200 μg ml-1 to 40 μg ml-1.19 Similarly, the addition of eugenol or Cinnamomum verum J. Preslreduced the MIC of fluconazole to 80 μg ml-1.19 Synergy was also observed against Aspergillus species suggesting broad spectrum antifungal activity.19 Strong synergism is also noted in studies of Mentha piperita L. and its components menthone and menthol with itraconazole against T. mentagrophytes,26as well as citronellol and geraniol from Pelargonium graveolens L’Hér combined with ketoconazole against Trichophyton spp.27

Some plant extracts are also reported to be effective against resistant strains of dermatophytes.  The extract of Pothomorphe umbellata (L.) yielded an MIC of 78 μg ml-1 against T. rubrum containing genes associated with multi-drug resistance.28 Cinnamaldehyde isolated from C. verum was also effective against fluconazole and itraconazole resistant strains of dermatophytes with an MIC of 40-80 μgml-1.19 Essential oil of Cymbopogon citratus (DC.) Stapf and citral also generated inhibited zones of diameter 24.7 – 32.6 mm against azole resistant strains of T. rubrum.29 The proposed mechanisms and utility of such plant extracts in overcoming drug-resistant fungi are discussed below.

Results 2:  Plants with in vivo anti-dermatophytic activity
Twenty-one plant extracts were evaluated using in vivo bioassays.  Of these, only 6 plant preparations have been tested in clinical trials, summarised in Table 1.  Tea tree oil was evaluated in four randomised controlled trials, of which two demonstrated significantly better outcomes compared to placebo, and were comparable to commercial antifungal preparations including topical butenafine and topical clotrimazole.30, 31 However, one randomized double-blind trial randomizing 104 patients with tinea pedis to 1% tolnaftate, placebo or 10% tea tree oil cream showed significantly lower mycological cure rates with tea tree oil (30%) compared to tolnaftate (85%).32  Nonetheless, tea tree oil was significantly better than placebo.32  Isolated encecalin from snake root (Ageratina pichinchensis (Kunth) R.M.King & H.Rob.) was evaluated in five small randomised, double-blind controlled trials in patients with tinea pedis and onychomycosis and showed comparability to topical ketoconazole and ciclopirox respectively.  In patients with onychomycosis, topical lacquer made from norway spruce (Picea abies (L.) H.Karst.)was as effective as 5% amorolfine (13% vs 5% cure, respectively), but significantly less effective than oral terbinafine in achieving mycological cure (56% at 10 months).33  Garlic (Allium sativum L.), snow gum (Eucalyptus pauciflora Sieber ex Spreng.) and Devil’s fig (Solanum chrysotrichum Schltdl.) have also been tested in clinically but are preliminary and of small size.34-36

The remaining plant extracts tested in vivo were animal studies (Appendix 2: click HERE), most commonly in guinea pigs, but also in mice, sheep and cattle.  Five studies used anthropophilic dermatophyte species.  Studies consistently demonstrated efficacy through both clinical cure and mycological cure, comparable to pharmacological preparations.  Effects were dose-dependent with negligible dermal irritation.  Synergistic activity was also observed in a study of twenty-four cattle with T. verrucosum infections exposed to enilconazole, N. sativa extract, or combined treatment of enilconazole and plant extract.  Combined treatment resulted in healing of all 8 cattle, whereas single agent enilconazole or N. sativa treatment resulted in healing in 5 and 6 animals respectively.22

Table 1. Summary of clinical trials of anti-dermophytic plants

Mechanism of action of natural anti-dermatophytic compounds
The anti-dermatophytic mechanism of action in plants is multi-modal and includes disruption to cell membranes and cell wall synthesis as well as inhibition of hyphal growth and spore germination.  These actions are mediated by abundant active plant compounds, of which phytochemical screening indicate the presence of phenolic compounds, terpenoids, terpenes, alkaloids, xanthones and glycosides including saponins, and have been well-characterised.45

Phenolic compounds are found abundantly in plants and include phenols, flavonoids, tannins, quinones, coumarins and phenolic acids.  They are extractable by water, methanol or acetate.46 Gallic acid has been shown to inhibit ergosterol biosynthesis by reducing activity of sterol-14α-demethylase P450 and squalene epoxidase in T. rubrum.47 Ergosterol content in the fungal membrane was significantly decreased at all tested concentrations of gallic acid (between 43.75 and 83.33 μg ml-1).47  Correlation between content of phenolic compounds and antifungal activity is observed in a study of Vitis vinifera L., where grape varieties Alphonse-Lavallee containing the highest flavon-3-ol content also exhibited the highest antifungal activity.48  Tannins, found in many plants including Mimosa tenuiflora Benth., Hypericum perforatum L., Moringa oleifera Lam.and Urtica dioica L., inhibit cell wall synthesis through formation of irreversible complexes with proteins.49

Saponins have been previously reported to cause leakage of protein and enzymes from the cell by complexing with sterols in the cell membrane.50 They were the most effective anti-dermatophytic compound in Polyscias fulva (Hiern) Harms.51   Saponins have also been studied in the context of Candida which have also concluded alteration to cell membranes as the main mechanism.52 Increased permeability to propidium iodide for Candida in a study by Pinto (2009) suggests that there is a primary lesion of the cell membrane leading to cell death.53

Terpenoid phenols also exhibit strong broad-spectrum antifungal activity.  They include eugenol, which was reported as a main constituent of thirteen antifungal plants, as well as thymol and cavacrol found in Thymus vulgaris L., T. pulegioides and Origanum vulgare L.  Essential oil of O. gratissimum containing 57.8% eugenol, viewed under transmission electron microscopy, caused morphological changes to dermatophyte hyphae, with damages to cell wall and membranes and expansion of endoplasmic reticulum.54  Flow cytometric studies with lemon thyme and active compounds thymol and cavacrol, showed lesion formation in the cytoplasmic membrane and a reduction on ergosterol content.25  Suggested mechanisms of cell membrane disruption and cell death occur include calcium stress (increased cytosolic calcium leading to loss of cell viability) and inhibition of the Target of Rapamyci n (TOR) pathway.55

Interference of hyphal growth and spore germination contributes to the anti-dermatophytic action of plant extracts.  Extract of Tetradenia riparia (Hochst.) showed strong inhibition and irregular growth pattern of hyphae through scanning electron microscopy.56 Additionally, essential oil volatiles of Agathosma betulina (P.J.Bergius) Pillansinhibited spore production of T. rubrum.57Further subcultures of mycelia did not result in growth suggesting strong fungicidal action due to irreversible damage.57 This is significant, as spores are asexual reproductive structures which can initiate skin infections and are responsible for transmission in the community.  The hydroalcoholic extract of Piper regnellii was further able to inhibit spore germination in a dose-dependent manner, and 7.8 μg ml-1 inhibited T. rubrum spore generation by 100%.57 Nail fragments that were saturated and immersed in P. regnellii extract at a concentration of 1.2 mg ml-1 and inoculated with spore suspension did not experience mycelial growth, whereas the nail fragments not exposed to the plant extract had vigorous growth.58

Other compounds investigated for their mechanism of action include monoterpenes, terpenoids generally and sesquiterpenoids.  Macrocarpal C, a sesquiterpenoid isolated from E. globulus, waseffective against T. mentagrophytes though several mechanisms including increased membrane permeability, increased intracellular reactive oxygen species and induction of apoptosis through DNA fragmentation.21 Monoterpenes found abundantly in essential oils include geranial, geraniol, citral and citronellol are suggested to mediate their antifungal activity through inhibition of spore production, and binding of ergosterol resulting in fungal cell membrane destabilisation.57, 59

In vivo anti-inflammatory and immunomodulatory actions of anti-dermatophytic compounds
In addition to direct anti-dermatophytic effects, plant compounds have anti-inflammatory and immunomodulatory effects, which can enhance treatment effects in vivo.  Extract of Salacia senegalensis (Lam.) DC had inhibitory effects against soybean 5-lipoxygenase, an important enzyme in the inflammatory and oxidative response in humans.60 Immunomodulation has also been proposed in studies where in vivo anti-dermatophyticefficacy were observed, but in vitro efficacy is not, by enhancement of immune self-resolution.  For instance, in guinea-pigs with induced M. canis dermatophytosis, U. dioica extract at 100 mg ml-1 concentration did not achieve in vitro activity, but an in vivo assay demonstrated efficacy comparable to terbinafine, and was significantly better than negative control.61 In another in vivo study of Astragalus verus Olivierin T. verrucosum infected guinea-pigs, 40% concentration was comparable to positive control terbinafine.  However, lesions improved in the negative control at 13 days suggesting resolution is partially contributed by immune response.  Immunomodulatory mechanisms of Astralagus were studied by Guo et al., (2016), showing dose-dependent inhibition of over-production of cytokines TNF-α, IL-1β, IL-6 and IFN-γ in LPS-stimulated macrophages.62

Current limitations in research, and future prospects
Despite numerous in vitro studies demonstrating antifungal activity, only a small proportion utilise rigorous methodology as required for robust evidence.  Cos et al. (2006) outline a set of parameters and efficacy criteria for high quality evaluation of anti-infective potentials of natural products.63 These include use of reference strains, in vitro models on the whole organism, cytotoxicity testing, dose ranges reflecting a practical inhibitory concentration, and use of positive and negative controls.  An endpoint criteria for all anti-infective bioassays was recommended as having usual IC50 values (the minimum drug concentration inhibiting 50% of fungal growth), below 100 μg ml-1,and below 25 μM for pure compounds.63 Most anti-fungal studies have reported MIC (the lowest drug concentration inhibiting visible fungal growth). However, endpoint criteria for antifungal efficacy and cytotoxicity assays are rarely stated in in vitro studies.  Considering this, the number of plants having significant anti-dermatophytic properties may be exaggerated.  Commonly utilised antimicrobial susceptibility testing methods include standardised protocols by CLSI or EUCAST, whilst some studies use agar well diffusion methods or poisoned food techniques.64

In vitro efficacy also may not translate into in vivo efficacy, particularly in humans.  Many fungal, host factors such as immunosuppression and compliance, suboptimal absorption and penetration are all clinically relevant.6 Importantly, penetration of antifungals into the stratum corneum and its persistence is important in achieving cure.  Most in vivo data is based on animal models rather than clinical trials, which may undermine clinical applicability given differences in virulence factors and immune responses.65 For example, T. mentagrophytes, a zoophilic species,tends to cause an acute inflammatory response whereas T. rubrum, an anthropophilic species,causes minimal inflammation.65 Clinical trials show some encouraging results but generally constitute insubstantial evidence, given limitations of small sample size and methodological flaws.

Possible adverse outcomes of plant therapies such as contact dermatitis17 should also be considered, in case of indiscriminate use for commercial purposes.  For example, plants belonging to Rutaceae, the citrus family, or Moraceae, can cause phytophotodermatitis owing to photosensitising compounds furocoumarins and psoralens.66 This can be clinically overlooked if the extract is not applied to sun-exposed areas, or are only momentarily used to prevent colonisation.67 Alternatively, these undesirable components can be removed, such as furocoumarin-free extracts of bergamot oil, which retained their anti-dermatophytic activity in in vitro studies. 68 In most animal and human studies of anti-dermatophytic plants, minimal to no serious adverse effects have been reported from topical application, noting small sample sizes.  For example, in one study evaluating 5% Melaleuca alternifolia oil in cream for toenail onychomycoses, four of 40 patients reported only mild inflammation.30 Nonetheless, the risk of adverse cutaneous effects to topical plant extracts in general should be acknowledged.  In one multi-centre study of 1274 patients using topical botanical products, 11% of patients reported adverse cutaneous reactions based on a questionnaire, and 16% showed positive reactions when tested in a botanical series.69 In studies using cell cytotoxicity assays, optimistic results may be seen with minimal reports of toxicity.  For example, in a study evaluating S. senegalensis leaves, human epidermal HaCaT keratinocytes experienced no detrimental effects at concentrations displaying anti-dermatophytic and anti-inflammatory properties.  Cytotoxic activity was also evaluated for 2.5 μL ml-1 A. major oil, β-ocimene and α-pinene using a haemolytic activity assay and found 10%, 10% and 15% haemolysis respectively.70 This shows promise for natural agents with high antifungal activity and low toxicity.  However, significantly more cytotoxic studies are required to establish stronger safety evidence for plant-based treatments.

Antifungal resistance is a key global health problem and innovation and testing of natural products holds enormous potential.  However, the mechanisms of plant extracts responsible for activity against drug resistance are not well investigated.  Inhibition of multidrug (MDR) efflux pumps, and normal cell communication (quorum sensing) have been described as some of the key mechanisms against bacterial MDR pathogens.71 Synergy between diverse plant constituents is suggested to play a key role in the effectiveness of herbal medicine in anti-microbial resistance.72 As previously discussed, the anti-fungal mode of action of plants is due to numerous potential bioactive compounds and therefore multiple targets.  Unlike agents with single constituents and targets, the presumed chances of development of resistance are lower with multiple targets. However, there is little research on whether fungi or other microbes will develop resistance against plants similar to the mechanisms of resistance evolved against current pharmaceuticals.  Scientific evaluation of complex synergistic interactions is furthermore a likely challenging and costly process, without fully developed technology to study these mechanisms.71

Significant synergistic antifungal activity with conventional antifungals highlights the potential for combined drug therapy.  For instance, the combination of essential oils with topical drugs can enhance penetration to deeper skin layers via abundant low molecular weight terpenes.73 Combined therapy may also reduce therapeutic doses, improving side effect profiles, mycological clearance and development of resistance.74

Despite the comprehensive search strategy used here it is likely many plant extracts with antifungal potential were not located, due to the innumerable diversity of the plant kingdom and ethnomedical studies not published in electronic databases.

Conclusions
Superficial fungal infections are highly prevalent and the prevalence of chronic and resistant cases is increasing, highlighting the need for novel anti-dermatophytic compounds.  Based on numerous in vitro studies, many plant extracts demonstrate anti-dermatophytic efficacy.  The plant extracts or isolated compounds have significant potential to be used in many contexts:  directly applied alone – particularly in third world countries without readily accessible commercial antifungal drugs; incorporated into existing antifungal drugs for synergistic action; or further explored as novel antifungal drugs.  Despite this, very few of these studies have had in vivo testing or clinical trials to assess their safety and effectiveness, although those conducted so far have been promising.  Further in vivo studies will enable exploration and investment into new clinically effective anti-dermatophytic compounds, which is essential in the face of emerging dermatophyte resistance.

Provenance:   Externally reviewed
Ethical Approval:  Not required
Disclosures:  None
Acknowledgements:  None

Corresponding Author: Dr Angela Mei, Sir Charles Gairdner Hospital, Nedlands, Perth, WA 6009, Australia. Email: angela.mei@health.wa.gov.au

REFERENCES

  1. Bongomin F, Gago S, Oladele RO, Denning DW. Global and multi-national prevalence of fungal diseases—estimate precision. J Fungi 2017; 3: 57.
  2. AL-Khikani FHO. Dermatophytosis a worldwide contiguous fungal infection: Growing challenge and few solutions. Biomed Biotech Res J (BBRJ). 2020; 4: 117.
  3. Lakshmipathy DT, Kannabiran K. Review on dermatomycosis: pathogenesis and treatment. Nat Sci 2010; 2: 726.
  4. Hayette M-P, Sacheli R. Dermatophytosis, trends in epidemiology and diagnostic approach. Curr Fungal Inf Rep 2015; 9: 164-179.
  5. Verma SB, Panda S, Nenoff P et al. The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features. Ind J Dermatol Venereol Leprol 2021; 87: 154-175.
  6. Khurana A, Sardana K, Chowdhary A. Antifungal resistance in dermatophytes: Recent trends and therapeutic implications. Fungal Genet Biol 2019; 132: 103255.
  7. Wingfield Digby SS, Hald M, Arendrup MC, Hjorth SV, Kofoed K. Darier Disease Complicated by Terbinafine-resistant Trichophyton rubrum: A Case Report. Acta Dermato-venereologica 2017; 97: 139-140.
  8. Hiruma J, Noguchi H, Hase M, et al. Epidemiological study of terbinafine-resistant dermatophytes isolated from Japanese patients. J Dermatol 2021; 48: 564-567.
  9. Saunte DML, Pereiro-Ferreirós M, Rodríguez-Cerdeira C et al. Emerging antifungal treatment failure of dermatophytosis in erope: take care or it may become endemic. J Eur Acad Dermatol Venereol 2021; 35: 1582-1586
  10. Manzano-Gayosso P, Mendez-Tovar LJ, Hernandez-Hernandez F, Lopez-Martinez R. Antifungal resistance: an emerging problem in Mexico. Gaceta Medica de Mexico 2008; 144: 23-26.
  11. Gu D, Hatch M, Ghannoum M, Elewski BE. Treatment-resistant dermatophytosis: A representative case highlighting an emerging public health threat. JAAD Int Case Rep 2020; 6: 1153-1155.
  12. Singh A, Masih A, Khurana A et al. High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene. Mycoses 2018; 61: 477-484.
  13. Shivanna R, Inamadar A. Clinical failure of antifungal therapy of dermatophytoses: Recurrence, resistance, and remedy. Ind J Drugs Dermatol 2017; 3: 1-3.
  14. Martinez-Rossi NM, Bitencourt TA, Peres NT et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018; 9: 1108.
  15. Gupta AK, Foley KA, Versteeg SG. New Antifungal Agents and New Formulations Against Dermatophytes. Mycopathologia 2016; 182: 127-141.
  16. Singh R, Allaie AH, Ganaie AA et al. Antifungal activity of medicinal plants with special reference to antidermatophytic activity: A review. Pharma Innovation J. 2017; 6: 251-259.
  17. Kumarasinghe S. Medicinal plants in skin diseases: a survey among ayurvedic practitioners in Kalutara, Sri Lanka. Sri Lanka J Dermatol 1999; 4: 15-20
  18. Aiemsaard J, Punareewattana K. Antifungal activities of essential oils of Syzygium aromaticum, Piper betle, and Ocimum sanctum against clinical isolates of canine dermatophytes. Science Asia 2017; 43: 223-228.
  19. Khan MSA, Ahmad I. Antifungal activity of essential oils and their synergy with fluconazole against drug-resistant strains of Aspergillus fumigatus and Trichophyton rubrum. Appl Microbiol Biotech 2011; 90: 1083-1094.
  20. Rajarajan S, Selvi Rao M. Estimation of the antibacterial activity in the seitz filtered aqueous extract from the ripe fruit, unripe fruit and leaf galls of Terminalia chebula (chebulic myroblan). Biomedicine 2004; 24: 7.
  21. Wong JH, Lau K-M, Wu Y-O et al. Antifungal mode of action of macrocarpal C extracted from Eucalyptus globulus Labill (Lan An) towards the dermatophyte Trichophyton mentagrophytes. Chinese Med. 2015; 10: 34.
  22. Balikci E. Antidermatophyte and antioxidant activities of Nigella sativa alone and in combination with enilconazole in treatment of dermatophytosis in cattle. Veterinární Medicína. 2016; 61: 539-545.
  23. d’Auria F, Laino L, Strippoli V et al. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J Chemotherapy. 2001; 13: 377-383.
  24. Pinto E, Gonçalves M-J, Cavaleiro C, Salgueiro L. Antifungal activity of Thapsia villosa essential oil against Candida, Cryptococcus, Malassezia, Aspergillus and dermatophyte species. Molecules 2017; 22: 1595.
  25. Pinto E, Pina-Vaz C, Salgueiro L et al. Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species. J Med Microbiol 2006; 55: 1367-1373.
  26. Tullio V, Roana J, Scalas D, Mandras N. Evaluation of the antifungal activity of Mentha x piperita (Lamiaceae) of Pancalieri (Turin, Italy) essential oil and its synergistic interaction with azoles. Molecules 2019; 24: 3148.
  27. Shin S, Lim S. Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp. J Appl Microbiol 2004; 97: 1289-1296.
  28. Rodrigues ER, Nogueira NGP, Zocolo GJ, et al. Pothomorphe umbellata: Antifungal activity against strains of Trichophyton rubrum. J Mycologie Med 2012; 22: 265-269.
  29. Khan MSA, Ahmad I. In vitro antifungal activity of oil of Cymbopogon citratus and citral alone and in combination with fluconazole against azole-resistant strains of Aspergillus fumigatus and Trichophyton rubrum. Pharmacog Com 2013; 3: 29.
  30. Syed TA, Qureshi ZA, Ali SM, Ahmad S, Ahmad SA. Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream. Trop Med Int Health 1999; 4: 284-287.
  31. Buck DS, Nidorf DM, Addino JG. Comparison of Two Topical Preparations for the Treatment of Onychomycosis: Melaleuca alternifolia. J Fam Practice 1994; 38: 605.
  32. Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: a randomized, placebo-controlled, blinded study. Australasian J Dermatol 2002; 43: 175-178.
  33. Sipponen P, Sipponen A, Lohi J, Soini M, Tapanainen R, Jokinen JJ. Natural coniferous resin lacquer in treatment of toenail onychomycosis: an observational study. Mycoses 2013; 56: 289-296.
  34. Ledezma E, Sousa LD, Jorquera A, et al. Efficacy of ajoene, an organosulphur derived from garlic, in the short‐term therapy of tinea pedis. Mycoses 1996; 39: 393-395.
  35. Herrera-Arellano A, Rodríguez-Soberanes A, de los Angeles Martínez-Rivera M, et al. Effectiveness and tolerability of a standardized phytodrug derived from Solanum chrysotrichum on Tinea pedis: a controlled and randomized clinical trial. Planta Medica. 2003; 69: 390-395.
  36. Shahi SK, Shukla AC, Bajaj AK, et al. Broad spectrum herbal therapy against superficial fungal Infs. Skin Pharmacol and Appl Skin Physiol 2000; 13: 60-64.
  37. Ledezma E, Marcano K, Jorquera A et al. Efficacy of ajoene in the treatment of tinea pedis: a double-blind and comparative study with terbinafine. J Amer Acad Dermatol 2000; 43: 829-832.
  38. Tong MM, Altman PM, Barnetson RS. Tea tree oil in the treatment of tinea pedis. The Australasian J Dermatol 1992; 33: 145-149.
  39. Auvinen T, Tiihonen R, Soini M, Wangel M, Sipponen A, Jokinen J. Efficacy of topical resin lacquer, amorolfine and oral terbinafine for treating toenail onychomycosis: a prospective, randomized, controlled, investigator‐blinded, parallel‐group clinical trial. Br J Dermatol 2015; 173: 940-948.
  40. Romero-Cerecero O, Rojas G, Navarro V, Herrera-Arellano A, Zamilpa-Alvarez A, Tortoriello J. Effectiveness and tolerability of a standardized extract from Ageratina pichinchensis on patients with tinea pedis: an explorative pilot study controlled with ketoconazole. Planta Medica 2006; 72: 1257-1261.
  41. Romero-Cerecero O, Zamilpa A, Jiménez-Ferrer E, Tortoriello J. Therapeutic effectiveness of Ageratina pichinchensis on the treatment of chronic interdigital tinea pedis: a randomized, double-blind clinical trial. J Alt Comp Medicine 2012; 18: 607-611.
  42. Romero-Cerecero O, Zamilpa A, Jiménez-Ferrer JE, Rojas-Bribiesca G, Román-Ramos R, Tortoriello J. Double-blind clinical trial for evaluating the effectiveness and tolerability of Ageratina pichinchensis extract on patients with mild to moderate onychomycosis. A comparative study with ciclopirox. Planta Medica 2008; 74: 1430-1435.
  43. Romero-Cerecero O, Román-Ramos R, Zamilpa A, Jiménez-Ferrer JE, Rojas-Bribiesca G, Tortoriello J. Clinical trial to compare the effectiveness of two concentrations of the Ageratina pichinchensis extract in the topical treatment of onychomycosis. J Ethnopharmacol 2009; 126: 74-78.
  44. Romero‐Cerecero O, Islas‐Garduño AL, Zamilpa A, Tortoriello J. Effectiveness of an encecalin standardized extract of Ageratina pichinchensis on the treatment of onychomycosis in patients with diabetes mellitus. Phytother Res 2020; 34: 1679-1686.
  45. Boulogne I, Petit P, Ozier-Lafontaine H, Desfontaines L, Loranger-Merciris G. Insecticidal and antifungal chemicals produced by plants: a review. Environ Chem Lett 2012; 10: 325-347.
  46. Musyimi D, Ogur J. Comparative assessment of antifungal activity of extracts from Eucalyptus globulus and Eucalyptus citriodora. Res J Phytochem 2008: 35-43.
  47. Li ZJ, Liu M, Dawuti G et al. Antifungal activity of gallic acid in vitro and in vivo. Phytother Res 2017; 31: 1039-1045.
  48. Simonetti G, D’Auria FD, Mulinacci N et al. Phenolic content and in vitro antifungal activity of unripe grape extracts from agro-industrial wastes. Nat Product Res 2019; 33: 803-807.
  49. Othman L, Sleiman A, Abdel-Massih RM. Antimicrobial Activity of Polyphenols and Alkaloids in Middle Eastern Plants. Front Microbiol 2019; 10: 911-911.
  50. Mert-Türk F. Saponins versus plant fungal pathogens. J Cell Mol Biol 2006; 5: 13-17.
  51. Njateng GSS, Gatsing D, Mouokeu RS, Lunga PK, Kuiate J-R. In vitro and in vivo antidermatophytic activity of the dichloromethane-methanol (1: 1 v/v) extract from the stem bark of Polyscias fulva Hiern (Araliaceae). BMC Complement Alt Medicine 2013; 13: 95.
  52. Soliman S, Alnajdy D, El-Keblawy AA, Mosa KA, Khoder G, Noreddin AM. Plants’ Nat products as alternative promising anti-Candida drugs. Pharmacog Rev 2017; 11: 104.
  53. Pinto E, Pina-Vaz C, Salgueiro L et al. Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species. J Med Microbiol 2006; 55: 1367-1373.
  54. Silva M, Oliveira Jr J, Fernandes O et al. Antifungal activity of Ocimum gratissimum towards dermatophytes. Mycoses 2005; 48: 172-175.
  55. Rao A, Zhang Y, Muend S, Rao R. Mechanism of Antifungal Activity of Terpenoid Phenols Resembles Calcium Stress and Inhibition of the TOR Pathway. Antimicrobial Agents and Chemotherapy 2010; 54: 5062.
  56. Endo EH, Costa GM, Nakamura TU, Nakamura CV, Dias Filho BP. Antidermatophytic activity of hydroalcoholic extracts from Rosmarinus officinalis and Tetradenia riparia. J de Mycologie Med 2015; 25: 274-279.
  57. Fajinmi OO, Kulkarni MG, Benická S et al. Antifungal activity of the volatiles of Agathosma betulina and Coleonema album commercial essential oil and their effect on the morphology of fungal strains Trichophyton rubrum and mentagrophytes. SA J Botany 2019; 122: 492-497.
  58. Koroishi AM, Foss SR, Cortez DAG, Ueda-Nakamura T, Nakamura CV, Dias Filho BP. In vitro antifungal activity of extracts and neolignans from Piper regnellii against dermatophytes. J Ethnopharmacol 2008; 117: 270-277.
  59. Gomes NG, Oliveira AP, Cunha D et al. Flavonoid composition of Salacia senegalensis (Lam.) DC. leaves, evaluation of antidermatophytic effects, and potential amelioration of the associated inflammatory response. Molecules 2019; 24: 2530.
  60. Mikaeili A, Karimi I, Modaresi M, Bagherinasab Z. Assessment of antidermatophytic activities of Urtica dioica L against Microsporum canis in a guinea pig model. Trop J Pharmaceut Res 2013; 12: 997-1002.
  61. Guo Z, Xu H-Y, Xu L, Wang S-S, Zhang X-M. In vivo and in vitro immunomodulatory and anti-inflammatory effects of total flavonoids of African J Trad Complement Alt Meds 2016; 13: 60-73.
  62. Miron D, Battisti F, Silva FK et al. Antifungal activity and mechanism of action of monoterpenes against dermatophytes and yeasts. Revista Brasileira de Farmacognosia 2014; 24: 660-667.
  63. Cos P, Vlietinck AJ, Berghe DV, Maes L. Anti-infective potential of Nat products: how to develop a stronger in vitro ‘proof-of-concept’. J Ethnopharmacol 2006; 106: 290-302.
  64. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: a review. J Pharmaceutical Anal. 2016; 6: 71-79.
  65. Achterman RR, White TC. Dermatophyte Virulence Factors: Identifying and analyzing genes that may contribute to chronic or acute skin Infs. Int J Microbiol 2012; 2012: 358305.
  66. Pathak MA. Phytophotodermatitis. Clinics in Dermatol 1986; 4: 102-121.
  67. Kumarasinghe S. Lime juice and soap inhibit growth of dermatophytes in vitro. Sri Lanka J Dermatol 2003; 7: 24-27.
  68. Sanguinetti M, Posteraro B, Romano L et al. In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes. J Antimicrob Chemotherapy 2007; 59: 305-308.
  69. Corazza M, Borghi A, Gallo R et al. Topical botanically derived products: use, skin reactions, and usefulness of patch tests. A multicentre Italian study. Contact Dermatitis 2014; 70: 90-97.
  70. Cavaleiro C, Salgueiro L, Gonçalves M-J, Hrimpeng K, Pinto J, Pinto E. Antifungal activity of the essential oil of Angelica major against Candida, Cryptococcus, Aspergillus and dermatophyte species. J Nat Medicines 2015; 69: 241-248.
  71. Vaou N, Stavropoulou E, Voidarou C et al. Towards advances in medicinal plant antimicrobial activity: A review study on challenges and future perspectives. Microorganisms 2021; 9: 2041.
  72. Mundy L, Pendry B and Rahman M. Antimicrobial resistance and synergy in herbal medicine. J Herbal Med 2016; 6: 53-58.
  73. Lopes G, Pinto E, Salgueiro L. Nat products: an alternative to conventional therapy for dermatophytosis? Mycopathologia 2017; 182: 143-167.
  74. Sahoo AK, Mahajan R. Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review. Ind Dermatol Online J 2016; 7: 77-86.
  75. Guerra-Boone L, Alvarez-Román R, Salazar-Aranda R et al. Antimicrobial and antioxidant activities and chemical characterization of essential oils of Thymus vulgaris, Rosmarinus officinalis, and Origanum majorana from northeastern México. Pakistan J Pharmaceutical Sci 2015; 28.
  76. Lima EdO, Gompertz OF, Giesbrecht A, Paulo MQ. In vitro antifungal activity of essential oils obtained from officinal plants against dermatophytes. Mycoses 1993; 36: 333-336.
  77. Koba K, Poutouli PW, Raynaud C, Sanda K. Antifungal activity of the essential oils from Ocimum gratissimum L grown in Togo. J Sci Res 2009; 1: 164-171.
  78. Tiwari T, Chansouria J, Dubey N. Antimycotic potency of some essential oils in the treatment of induced dermatomycosis of an experimental animal. Pharmaceutical Biol 2003; 41: 351-356.
  79. Balakumar S, Rajan S, Thirunalasundari T, Jeeva S. Antifungal activity of Ocimum sanctum(Lamiaceae) on clinically isolated dermatophytic fungi. Asian Pacific J Tropical Med 2011; 4: 654-657.
  80. Sharma M, Sharma M. Antimicrobial potential of essential oil from Mentha piperita against anthropophilic dermatophytes. J Essential Oil Bearing Plants 2012; 15: 263-269.
  81. Mugnaini L, Nardoni S, Pistelli L et al. A herbal antifungal formulation of Thymus serpillum, Origanum vulgare and Rosmarinus officinalis for treating ovine dermatophytosis due to Trichophyton mentagrophytes. Mycoses 2013; 56: 333-337.
  82. Park M-J, Gwak K-S, Yang I et al. Antifungal activities of the essential oils in Syzygium aromaticum (L.) Merr. Et Perry and Leptospermum petersonii Bailey and their constituents against various Dermatophytes. J Microbiol 2007; 45: 460-465.
  83. Rana IS, Rana AS, Rajak RC. Evaluation of antifungal activity in essential oil of the Syzygium aromaticum (L.) by extraction, purification and analysis of its main component eugenol. Brazil J Microbiol 2011; 42: 1269-1277.
  84. Nenoff P, Haustein UF, Brandt W. Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro. Skin Pharmacol 1996; 9: 388-394.
  85. Hammer KA, Carson CF, Riley TV. In vitro activity of Melaleuca alternifolia (tea tree) oil against dermatophytes and other filamentous fungi. J Antimicrob Chemother 2002; 50: 195-199.
  86. Flores FC, de Lima JA, Ribeiro RF et al. Antifungal activity of nanocapsule suspensions containing tea tree oil on the growth of Trichophyton rubrum. Mycopathologia 2013; 175: 281-286.
  87. Benger S, Townsend P, Ashford RL, Lambert P. An in vitro study to determine the minimum inhibitory concentration of Melaleuca alternifolia against the dermatophyte Trichophyton rubrum. The Foot 2004; 14: 86-91.
  88. Kindu G, Mekonen M, Ageze E, Abebaw M, Workie A, Getnet B. Antifungal efficiency of three traditional medicinal plants against Trichophyton rubrum. World News of Nat Scis 2019; 25: 15-21.
  89. Biasi-Garbin RP, Demitto FdO, Amaral RCR et al. Antifungal potential of plant sepcies from Brazilian Caatinga against dermatophytes. Rev Inst Med Trop Sao Paulo 2016; 58: 18-18.
  90. Moghimipour E, Ameri A, Saudatzadeh A, Salimi A, Siahpoosh A. Formulation of an antidermatophytic cream from hydro-alcoholic extract of Eucalyptus camaldulensis Jundishapur J Nat Pharm Prod 2009; 4: 32-40.
  91. Essien JP, Akpan EJ. Antifungal activity of ethanolic leaf extract of Eucalyptus camaldulensis Against ringworm pathogens. Global J Pure Appl Sci 2004; 10: 37-41.
  92. Falahati M, Omidi Tabrizib N, Jahaniani F. Anti dermatophyte activities of Eucalyptus camaldulensis in comparison with Griseofulvin. Iran J Pharmacol Ther 2005; 4: 80-80.
  93. Baptista EB, Zimmermann-Franco DC, Lataliza AAB, Raposo NRB. Chemical composition and antifungal activity of essential oil from Eucalyptus smithii against dermatophytes. Revista da Sociedade Brasileira de Medicina Tropical 2015; 48: 746-752.
  94. Lozoya X, Navarro V, Arnason JT, Kourany E. Experimental evaluation of Mimosa tenuiflora (willd.) poir. (Tepescohuite) I. Screening of the antimicrobial properties of bark extracts. Archivos de Investigacion Medica 1989; 20: 87-93.
  95. Sagar K, Vidyasagar G. Anti-dermatophytic activity of some traditionally used medicinal plants of North Karnataka Region. J Appl Pharmaceutical Sci 2013; 3: 77.
  96. Kagne R, Rajbhoj B. In vitro evaluation of various extracts of Acacia nilotica (L.) del. against human pathogenic fungi. J Pharmacog Phytochem 2019; 8: 2366-2368.
  97. El-Ashmawy W, Elhafez E, El-Saeed H. Clinical study on dermatophytosis in calves with in vitro evaluation of antifungal activity of Bergamot oil. Adv Animal Vet Sci 2015; 3: 34-39.
  98. Balakumar S, Rajan S, Thirunalasundari T, Jeeva S. Antifungal activity of Aegle marmelos (L.) Correa (Rutaceae) leaf extract on dermatophytes. Asian Pac J Trop Biomed 2011; 1: 309-312.
  99. Apisariyakul A, Vanittanakom N, Buddhasukh D. Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae). J Ethnopharmacol. 1995; 49: 163-169.
  100. Sharma M, Sharma R. Synergistic Antifungal Activity of Curcuma longa (Turmeric) and Zingiber officinale (Ginger) Essential Oils Against Dermatophyte Infections. J Essential Oil Bearing Plants 2011; 14: 38-47.
  101. Jankasem M, Wuthi-udomlert M, Gritsanapan W. Antidermatophytic properties of ar-turmerone, turmeric oil, and Curcuma longa ISRN Dermatol 2013; 2013.
  102. Zeng H, Chen X, Liang J. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species. J Med Microbiol 2015; 64: 93-103.
  103. Gurgel LA, Sidrim J, Martins DT, Cechinel Filho V, Rao VS. In vitro antifungal activity of dragon’s blood from Croton urucurana against dermatophytes. J Ethnopharmacol 2005; 97: 409-412.
  104. Prasad CS, Shukla R, Kumar A, Dubey NK. In vitro and in vivo antifungal activity of essential oils of Cymbopogon martini and Chenopodium ambrosioides and their synergism against dermatophytes. Mycoses 2010; 53: 123-129.
  105. Liao Y, Yang D, Li Y, Ma D. Antifungal activity of volatile oil from invasive weed, Chenopodium ambrosioides, on dermatophytes. Southwest China J Agric Sci 2010; 23: 863-865.
  106. Bajpai VK, Yoon JI, Kang SC. Antifungal potential of essential oil and various organic extracts of Nandina domestica Thunb. against skin infectious fungal pathogens. Appl Microbiol and Biotech 2009; 83: 1127-1133.
  107. Natarajan V, Venugopal PV, Menon T. Effect of Azadirachta indica (neem) on the growth

pattern of dermatophytes. Ind J Med Microbiol 2003; 21: 98-101.

  1. Ospina Salazar DI, Hoyos Sanchez RA, Orozco Sanchez F, Arango Arteaga M, Gomez Londono LF. Antifungal activity of neem (Azadirachta indica: Meliaceae) extracts against dermatophytes. Acta Biológica Colombiana 2015; 20: 181-192.
  2. Radhika S, Michael A. In vitro antifungal activity of leaf extracts of Azadirachta indica. Int J Pharm Sci. 2013; 5: 723-725.
  3. Chuang P-H, Lee C-W, Chou J-Y, Murugan M, Shieh B-J, Chen H-M. Anti-fungal activity of crude extracts and essential oil of Moringa oleifera Bioresource Technol 2007; 98: 232-236.
  4. Zaffer M, Ganie SA, Gulia SS, Yadav S, Singh R, Ganguly S. Antifungal Efficacy of Moringa oleifera American J Phytomed Clin Ther 2015; 3: 28-33.
  5. Wagini N, Abbas MS, Soliman AS, Hanafy YA, Badawy El-Saady M. In vitro and in vivo anti-dermatophyte activity of Lawsonia inermis(henna) leaves against ringworm and its etiological agents. Am J Clin Exp Med 2014; 2: 51-58.
  6. Sharma K, Saikia R, Kotoky J, Kalita J, Devi R. Antifungal activity of Solanum melongena L, Lawsonia inermis and Justicia gendarussa B. against dermatophytes. Int J PharmTech Res 2011; 3: 1635-1640.
  7. Ekwealor C, Oyeka C. In vitro anti-dermatophyte activities of crude methanol and aqueous extracts of Lawsonia inermis. J. Pharm Sci. Drug Res 2015; 7: 59-62.
  8. Suleiman EA, Mohamed EA. In vitro activity of Lawsonia inermis (Henna) on some pathogenic fungi. J Mycology 2014; 2014.
  9. Natarajan V, Mahendraraja S, Thangam M. Anti-dermatophytic activities of Lawsonia alba. Biomedicine 2000; 20: 243-245.
  10. Foss SR, Nakamura CV, Ueda-Nakamura T, Cortez DA, Endo EH, Dias Filho BP. Antifungal activity of pomegranate peel extract and isolated compound punicalagin against dermatophytes. Ann Clin Microbiol Antimicrobials 2014; 13: 32.
  11. Aguilar-Guadarrama B, Navarro V, Leon-Rivera I, Rios MY. Active compounds against tinea pedis dermatophytes from Ageratina pichinchensis bustamenta. Nat Product Res 2009; 23: 1559-1565.
  12. Njateng GSS, Du Z, Gatsing D et al. Antifungal properties of a new terpernoid saponin and other compounds from the stem bark of Polyscias fulva Hiern (Araliaceae). BMC Complemen Alt Med 2015; 15: 25.
  13. Mikaeili A, Modaresi M, Karimi I, Ghavimi H, Fathi M, Jalilian N. Antifungal activities of Astragalus verus Olivier. against Trichophyton verrucosum on in vitro and in vivo guinea pig model of dermatophytosis. Mycoses 2012; 55: 318-325.
  14. Rautio M, Sipponen A, Lohi J, Lounatmaa K, Koukila-Kähkölä P, Laitinen K. In vitro fungistatic effects of Nat coniferous resin from Norway spruce (Picea abies). Eur J Clin Microbiol Inf Dis 2012; 31: 1783-1789.
  15. Rubini B, Shanthi G, Soundhari C, Rajarajan S. Antifungal activity of Terminalia chebula and Terminalia catappa on two dermatophytes. Open Access J Medicinal and Aromatic Plants 2013; 4: 15.
  16. Singh G, Kumar P, Joshi SC. Treatment of dermatophytosis by a new antifungal agent ‘apigenin’. Mycoses 2014; 57: 497-506.
  17. Kishore N, Mishra A, Chansouria J. Fungitoxicity of essential oils against dermatophytes: Die Fungitoxizität ätherischer Öle gegen Dermatophyten. Mycoses 1993; 36: 211-215.
  18. Mbakwem-Aniebo C, Onianwa O, Okonko I. Effects of Ficus exasperata Vahl on common dermatophytes and causative agent of Pityriasis Versicolor in rivers state, Nigeria. American J Dermatol Venereol 2012; 1: 1-5.
  19. Mahmoudvand H, Sepahvand A, Jahanbakhsh S, Ezatpour B, Mousavi SA. Evaluation of antifungal activities of the essential oil and various extracts of Nigella sativa and its main component, thymoquinone against pathogenic dermatophyte strains. J de Mycologie Med 2014; 24: e155-e161.
  20. AlJabre SHM, Randhawa MA, Alakloby OM, Alzahrani AJ. Thymoquinone inhibits germination of dermatophyte arthrospores. Saudi Med J 2009; 30: 443-445.
  21. Khosravi RA, Shokri H, Farahnejat Z, Chalangari R, Katalin M. Antimycotic efficacy of Iranian medicinal plants towards dermatophytes obtained from patients with dermatophytosis. Chinese J Nat Med 2013; 11: 43-48.
  22. Sunita M, Meenakshi S. Chemical composition and antidermatophytic activity of Nigella sativa essential oil. African J Pharm Pharmacol 2013; 7: 1286-1292.
  23. Rahman A, Al-Reza SM, Siddiqui SA, Chang T, Kang SC. Antifungal potential of essential oil and ethanol extracts of Lonicera japonica against dermatophytes. EXCLIJ 2014; 13: 427.
  24. Larypoor M, Akhavansepahy A, Rahimifard N, Rashedi H. Antidermatophyte activity of the essential oil of Hypericum perforatum of North of Iran. J Medicinal Plants 2009; 8: 110-117
  25. Tocci N, Simonetti G, D’Auria FD, et al. Root cultures of Hypericum perforatum angustifolium elicited with chitosan and production of xanthone-rich extracts with antifungal activity. Appl Microbiol Biotech. 2011; 91: 977-987.
  26. Massiha A, Muradov PZ. Comparison of antifungal activity of extracts of ten plant species and griseofulvin against human pathogenic dermatophytes. Zahedan J Res Med Sci 2015; 17
  27. Ali‐Shtayeh M, Abu Ghdeib SI. Antifungal activity of plant extracts against dermatophytes. Mycoses 1999; 42: 665-672.
  28. Premkumar V, Shyamsundar D. Antidermatophytic activity of Pistia stratiotes. Ind J Pharmacol 2005; 37: 127.
  29. Nejad BS, Deokule SS. Anti-dermatophytic activity of Drynaria quercifolia (L.) J. Smith. Jundishapur J Microbiol 2009; 2: 25.
  30. Mahule A, Rai P, Ghorpade DS, Khadabadi S. In vitro antifungal activity of ethanol fractions of Argyreia nervosa (Burm. f.) Boj. Leaves 2012; 3: 48-54.
  31. Yongabi K, Dukku U, Agho M, Chindo I. Studies on the Antifungal properties of Urtica dioica uritcaceae (Stinging Nettle). J Phytomed Ther 2000; 5: 39-43.
  32. Aremu SO, Iheukwumere CC, Umeh EU, Olumuyiwa EO, Fatoke B. In vitro antimicrobial efficacy study of borreria verticillata stem bark extracts against some dermatophytes and drug resistant pathogens. Int J Scientific Res Pub 2019; 9: 529 – 537
  33. Aliyu RM, Abubakar MB, Kasarawa AB et al. Efficacy and phytochemical analysis of latex of Calotropis procera against selected dermatophytes. J Intercultural Ethnopharmacol 2015; 4: 314.
  34. Goyal S, Kumar S, Rawat P, Dhaliwal N. Antifungal activity of Calotropis procera towards dermatoplaytes. Int J Adv Pharm Biol Chem 2013; 2: 2277-4688.
  35. Verma R, Satsangi G, Shrivastava J. Susceptibility of a weed Calotropis procera (Ait.) against clinical isolates of dermatophytes. J Medicinal Plants Res 2011; 5: 4731-4739.
  36. Kuta F. Antifungal effect of Calotropis procera stem bark on Epidermophyton flocosum and Trichophyton gypseum. African J Biotech 2008; 7.
  37. Soković M, Glamočlija J, Ćirić A et al. Antifungal activity of the essential oil of Thymus vulgaris and thymol on experimentally induced dermatomycoses. Drug Development and Industrial Pharmacy 2008; 34: 1388-1393.

 

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AUTHOR INFORMATION

Dr Angela Mei

OCCUPATION
Resident Medical Officer
INSTITUTIONAL AFFILIATIONS
Sir Charles Gairdner Hospital, Nedlands, Perth 6009, Australia.

Dr Bernadette Ricciardo

OCCUPATION
Consultant Dermatologist
INSTITUTIONAL AFFILIATIONS
Dept. of Dermatology, Fiona Stanley Hospital, Murdoch WA 6150 Australia.
ORCID: 0000-0001-5902-040X
Wesfarmers Centre for Vaccines and infectious Diseases, Telethon Kids Institute, Nedlands, WA 6009.

School of Medicine, University of Western Australia, Crawley WA 6009 Australia.

Dr Edward Raby

OCCUPATION
Clinical Microbiologist
INSTITUTIONAL AFFILIATIONS
Department of Infectious Diseases, Fiona Stanley Hospital.
ORCID: 0000-0003-1671-6188

Dr S Prasad Kumarasinghe

OCCUPATION
Consultant Dermatologist
INSTITUTIONAL AFFILIATIONS
School of Medicine, University of Western Australia, Crawley WA 6009 Australia.

Dept. of Dermatology, Fiona Stanley Hospital, Murdoch WA 6150 Australia.

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