Background

Fungal infections are divided into two types: primary and opportunistic. Opportunistic infections occur mainly in immunocompromised hosts, but primary infections may also occur in hosts with a healthy immune system. Besides that, fungal infections can be systemic or local [1]. Fungi can evade immune system responses via different processes, including recombination, mitosis, and expression of genes involved in oxidative stress responses, and, therefore, can cause chronic fungal diseases. Despite the expansion of health care facilities, the incidence rate of fungal infections is still very high. For example, fungal infections are the fourth leading skin diseases worldwide. In 1984, 984 million people suffered from fungal skin infections. Secondary infection, deafness, tinea, and skin lesions are some of the complications due to fungal infections [2].

Dermatophytes represent the main cause of cutaneous diseases. Dermatophytes attack keratinized tissues, such as nail, hair, and stratum corneum, causing dermatophytosis [1]. Dermatophytosis is very common and can be life-threatening for the elderly and immunocompromised people. The highest prevalence of this disease is seen in people between the ages of 20-31 years. Dermatophytes cause skin scaling, create gray loops in the skin, and cause hair loss and loosening and nail deformities [3]. Dermatophytes have three genera: Microsporum, Tricophyton, and Epidermophyton, whose reservoirs are soil, animals, and humans [4].

The cloning process of dermatophytes is associated with the release of proteolytic enzymes and spontaneous stimulation of the host inflammatory responses, and causes dermatophytosis or tinea (ringworm). Inflammatory symptoms at the infection site include redness, swelling, and alopecia. Swelling causes transmission of infection to other parts of the body that causes circular lesions. The severity of infection due to dermatophytes depends on age, surrounding temperature, humidity level, and health and social conditions [5]. Different genera of dermatophytes have many phenotypic and genotypic similarities that make their detection challenging. Colony testing, microscopic examination of morphology, genotypic tests, and in some cases, detection of nutritional requirements, temperature tolerance, and urease production are used to detect dermatophytes [6]. Some parts of the body, such as nail subdistal region and area between the fingers, are more prone to dermatophytosis because they are exposed to the fungus in the long-term and provide certain factors, such as sugar and pH, that are required for the fungus [5].

Dermatophytes can induce increased immediate, delayed, or mediated cell susceptibility. In infected people with a normal immune system, response to increased susceptibility is induced within 30 days and is spontaneously recovered after 50 days. Dermatophyte distribution is different across the world [5]. In the past half-century, Tricophyton rubrum has been the most common dermatophyte, and in poor developing countries, Mycosis is endemic and affects a large number of children. Epidermophyton floccosum was common during two decades, i.e. 1980-1990, and among the isolated dermatophytes, is the leading dermatophyte in Iran with 31.4% prevalence [7][8]. In eastern and southern Europe, low quality of life has caused increased infection with animal-friendly dermatophytes. As well, urbanism, contacts, and travels have led to increased prevalence of T. rubrum [9].

Medicinal plants have long been used to treat different diseases in developed and developing countries [10]-[13]. In recent years, medicinal plants have also attracted much attention because their uses have had many benefits, such as decreased expenses and fewer side effects [14]-[17]. Use of plant-based products to fight fungal, bacterial, and parasitic infections has also been considered as an effective approach [7][8]. Moreover, certain measures can be taken to produce drugs by identifying the active compounds of the plants [18][19]. The antifungal effects of some plants, such as ginger, Narcissus tazetta, Myrtus communis, dill, cilantro, garlic, onions, henna, oak, black beans and thyme, on fungal infections have already been demonstrated. Flavonoids, alkaloids, tannins, citronellol , geraniol, thymoquinone, and phenolic compounds are some of the antifungal or other microbial active compounds found in these plants [20][21]. This review article was conducted to report medicinal plants with anti-dermatophytosis properties.

Materials and Methods

We searched the keywords “Medicinal plants”, “Traditional medicine” with the keyword “Dermatophytosis” in the Google Scholar, PubMed, Science Direct, and Scopus databases.

After the first search, seventy-six articles were found to be relevant.

After exclusion of duplicates and irrelevant articles by checking article topics, 54 articles were selected. After reviewing abstracts of the remaining articles, 23 articles were included in this study.

Results

Fungal diseases are known as mycoses, according to the National Institute of Allergies and Infectious Diseases. Mycoses can affect various parts of the body, including body hair, lungs, nervous system, nails, and skin. The most common types of fungal infections are tinea infections and fungal infections of hair, skin or nails; these include athlete’s foot, jock itch, candida, and vaginal yeast infections. Fungal skin infections usually involve itching, skin discoloration, and changes in skin texture in the affected area.

Certain herbs are known as fungicides, or agents that destroy fungi and their spores. Since fungal infections are often tenacious and difficult to eliminate, several different medicines may be necessary to provide therapeutic relief. On the other hand, the routine fungicides like azoles have several side effects.

According to findings of the study herein, Azadirachta indica, Capparis spinosa, Anagallisavensis, Juglans regia, Inula viscosa, Phagnalon rupestre, Plumbago europaea, Ruscus aculeatus, Ruta chalepensis, Salvia fruticosa, Artemisia judaica, Ballota undulate, Cleome amblyocarpa, Peganum harmala, Teucrium polium, Aegle marmelos, Artemisia sieberi, Cuminum cyminum, Foeniculum vulgare, Heracleum persicum, Mentha spicata, Nigella sativa, and Rosmarinus officinalis are the most effective plants on dermatophytes that have been identified to date. Various form of extracts and essences of these plants were found to have growth inhibition or killing effect on dermatophytosis agents and their pathogenicity. Most of the plants belong to family Lamiaceae. All the plants have very good effects against dermatophytosis agents in either minimum inhibitory concentration test (MIC) or in minimum fungicidal concentration test (MFC), and other tests. Even some clinical dermatophytosis isolates show drug resistance from these plants. Table 1 shows further information about the botanical names, studied doses, and effects of these plants.

Discussion

According to the findings of the present study, A. indica, C. spinosa, A . avensis, J. regia, I. viscosa, P. rupestre, P. europaea, R. aculeatus, R. chalepensis, S. fruticosa, A. judaica, B. undulate, C. amblyocarpa, P. harmala, T. polium, A. marmelos, A. sieberi, C. cyminum, F. vulgare, H. persicum, M. spicata, N. sativa, and R. officinalis are the most effective plants on dermatophytes that have been identified to date. Overall, many of the sulfuric compounds, phenolic compounds, flavonoids, tannins, and anthocyanins in the plants cause antifungal effects. Here, in this review article, we touched on the active compounds of the reported plants according to phytochemical investigations. Eugenol is the main antifungal compound of O. sanctum [45]. Tetranortriterpenoid has been demonstrated to be main antifungal compound present in A. indica, while some other compounds, such as 6-deacetylnimbin, azadiradione, nimbin, salannin and epoxyazadiradione, are considered main active compounds of A. indica with antifungal activity [46]. Moreover, rutin, tocopherols, carotenoids, and vitamin C have been confirmed to be the antimicrobial and antifungal compounds of C. spinosa. Glycosidic saponin is the antifungal active compound of A. arvensis [47]. A study on C. amblyocarpa demonstrated that this plant contained a number of valuable fatty acids, such as stearic acid, oleic acid, and linoleic acid. In addition, C. amblyocarpa contained some other compounds, including vitamin C, gallic acid, gallotannins and iridoid, that have many properties, namely antifungal [48]. In A. judaica, certain antifungal active compounds were identified, including camphor, piperitone, and ethyl cinnamate [49], while 3-hydroxy-(5- beta)-androst-2-en-17-one, 4-(1,1-dimethyl)-1,2-benzenediol, and desoxy-dihydro-isostevilo were reported to be the active compounds of B. undulate [16]. Limonene, 2,4-di-tetr-butyl, and p-cymene were the most important antifungal compounds of T. polium [14]. Moreover, 2-isopropenyl- 4-methyl-1-oxa-cyclopenta[b]anthracene-5,10-dione, imperatorin, plumbagin, and b-sitosterol glucoside are some of the main antifungal compounds of A. marmelos [15].

Furthermore, alkaloids, flavonoids, glycosides, and tannins are the main antifungal compounds of P. harmala [50]. Investigations have demonstrated that the main active antifungal compounds present in J. regia are naphthoquinones and flavonoids [51]. Carvacrol and thymol are the most important active compounds of P. rupestre [52]. Azoles and flavonoids, especially sesquiterpenes, are the most important antifungal compounds of I. viscosa [53]. Carvacrol and thymol are the active compounds of S. fruticosa [8], and 2-nonanone and 2-undecanone are the active compounds of R. chalepensis [54]. The active compounds of P. europaea are plumbagin, 1- octane-ly3-acetate, limonene, and nonanal [55]. Certain active compounds, such as vitexin, rutin, isoquercitrine, nicotiflorin, and schaftoside, are present in R. aculeatus [56].

Thymoquinone with antifungal activity has been shown to be one of the important active compounds of N. sativa [57], while spearmint oil and (S)-(-)-carvone are the active compounds of M. spicata [58]. Additional studies have demonstrated that cuminaldehyde and pinenes were among the active compounds of C. cyminum [59]. In F. vulgare, certain compounds, like (E)- anethole and fenchone, had antifungal properties [60], in A. sieberi, α-thujone and β-thujone were found to be antifungal active compounds [61], and in H. persicum, hexyl butyrate and p-cymene were the important antifungal compounds [62]. Meanwhile, the active compounds of R. officinalis

were 1.8-cineole and α-pinene [63]. As can be seen, most of the effective components of these plants are from phenolic compounds, which besides having antifungal activities have mostly antioxidant properties [64]-[69]. Antioxidants are beneficial compounds which are effective against a wide variety of diseases [70]-[75]. Hence, each individual plant, other than for treating fungal infections, might be used for other diseases, such as gastrointestinal, cardiovascular and/or immunological disorders [76]-[81]. These group of plants also may have antidotal activity [82].

Due to a high prevalence of dermatophytosis and high speed of acquiring this disease around the world, especially in low-income regions and developing countries, it is necessary to investigate these drugs as well as pharmaceutical and antifungal agents with anti-dermatophytes effects. Indeed, there are life-threatening side effects due to these chemical drugs. The findings of this study may have many implications, such as in the development of new drugs or in paving the way to conduct additional studies, particularly related to mechanism.

Conclusion

Common medications used to treat fungal infections, especially those with systemic use, have many proven side effects. There is also drug resistance in many fungal species to commonly used drugs, and this resistance has grown mostly in recent years. Medicinal plants are valuable sources of effective antifungal and therapeutic agents which can be useful in the treatment of various diseases, including fungal infections. These plants have a broad use in traditional medicine and complementary medicine, in the unprocessed form, and in modern medicine, either in processed or purified active substance form. Further research studies are required for developing new drugs from these valuable sources.

Open Access

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List of abbreviations

MIC: Minimum inhibitory concentration; microg/mL: Microgram per milliliter

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Competing interests

The authors declare that they have no conflicts of interest.

Funding

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Authors’ contributions

All of the authors have participated in manuscript preparation, Manuscript review, Design, Literature search, Manuscript editing. All authors read and approved the final version of manuscript.