Have you felt a tingle between your toes or an itch on your scrotum? Before you search Dr. Google for the cause, the itch could be caused by Dermatophytes. Dermatophytes are a group of pathogenic fungi responsible for most fungal skin infections. This includes everything from Athlete’s foot to ring worm, thrush and fungal nail infections. They thrive on the keratin that makes up our protective layers of skin, hair and nails. Dermatophytes affect one billion people each year, with the highest rates in tropical regions with moist climates. They affect humans and animals, although different species have different natural hosts.
Resistance to antifungal drugs is rising
Recent concerning data suggest that there are increasing rates of chronic, relapsing cases of fungal skin infections caused by dermatophytes. Commonly prescribed antifungal creams and agents fail to treat infections due to growing resistance. Although already endemic in some parts of India, cases of multi-drug resistance have been reported in Japan, European countries, Iran, Mexico, and the US. This development has an unclear cause, but it may be due to widespread misuse of readily available antifungal creams with steroids, poor compliance, and limited drug action and targets mechanisms.
Plants may hold the key to combating drug resistance
Since prehistoric times, natural products in the form of plants, animals, or microorganisms have been utilized to alleviate common disorders. These have been utilised primarily in traditional medicine or ethnomedicine for thousands of years. This has been replaced largely by modern medicine in most countries but still provides a valuable resource for identifying and screening new antimicrobial compounds. For example, artemisinin, a revolutionary drug for treating malaria, was developed from the plant qinghao. Qinghao was used in traditional medicine for over 2000 years before the isolation of the active compound. Certainly, many lifesaving and widely used drugs today are derived from plants—such as aspirin from willow bark, morphine from the opium plant—and the list is endless.
Because plants develop their own natural defense systems to avoid infection from other bacteria, fungi, and viruses, they provide a limitless source for new antimicrobial compounds.
Discovering cures from laboratory greenhouses
Laboratory-based testing demonstrated that seventy plant extracts exhibited antifungal properties, and of these, twenty-one were tested in animal or human studies. These plants were identified worldwide and investigated often based on their uses in traditional medicine. These included well-known plants such as rosemary, thyme, tea tree oil, oregano oil, clove, garlic, eucalyptus, cinnamon, henna and holy basil.
The ability of the compound to inhibit fungal growth was measured by mixing fungi and different concentrations of plant extracts to find the lowest concentration of the plant extract that blocked the visible growth of fungi. Plant extracts were compared to commercial drugs used as controls, which showed slightly less or equal antifungal activity. Nevertheless, they were significantly better than no treatment.
A proportion of studies also went on to isolate the most effective antifungal component, which showed consistently greater antifungal activity compared to their crude forms. For example, a compound isolated from the Tasmanian blue gum, denoted ‘Macrocarpal C’, had a similar level of antifungal activity compared to commercial antifungal drugs Lamisil® and nystatin.
Other notable findings include plant compounds being effective against resistance strains of dermatophytes. For example, the alcoholic extract of Pothomorphe umbellate, a native Brazillian plant, showed effectiveness against strains of Trichophyton rubrum with genes associated with multi drug resistance. Cinnamaldehyde, a naturally occurring product of cinnamon, was also able to effectively inhibit drug-resistant fungi. Cinnamaldehyde was also remarkable for its ability to synergistically interact with fluconazole, a commonly used antifungal pharmaceutical: the addition of the plant extract enhanced the ability of fluconazole to reduce fungal growth significantly.
Animal based studies and limited human studies show therapeutic potential
Many animal studies, and a few human based clinical trials have also shown promising results. Tea tree oil is one of the most well-known treatments for fungal skin infections, and it has been shown to be as effective as topical antifungal drugs. Compounds isolated from common plants such as snake roots, Norway spruce, garlic, snow gum, and devil’s fig showed promising results.
How do they work?
These plants have been shown to work against fungus in many different ways through various active plant compounds. For example, eugenol is an active plant chemical common to many plants like thyme and oregano. When viewed under a microscope, these compounds have been shown to cause damage to the protective cellular fungal membrane, allowing leakage of its contents and ultimately causing cell death. In addition, plants have been shown to block spore production, which is the main reproductive structure involved in disease transmission in the community, highlighting the many routes plants can combat fungi. In addition, it’s not surprising that plants also have many other beneficial side effects on skin in animal and human studies, with many studies suggesting anti-inflammatory effects and effects on the body’s immune system’s ability to respond to fungal infections.
Where to from here?
In the face of emerging dermatophyte resistance and ever-growing cases of chronic, treatment-unresponsive fungal infections, a global response to this public health threat is required. Investment into further research for new antifungal agents should be encouraged, where plant compounds provide an extensive, virtually limitless source of antifungal compounds. Multiple innovation pathways exist: direct application alone, particularly in under-resourced countries without readily available access to commercial antifungal drugs, combination with existing pharmaceuticals, or further isolation and exploration as novel antifungal drugs.
Mei, A., Ricciardo, B., Raby, E. and Kumarasinhe S.P. (2022) Plant-based therapies for dermatophyte infections, Tasman Medical Journal, 4(3), pp. 21-37.