Lamiaceae Plants Put the 'Fun' in Antifungal

Fungi

Many years ago, fungi were classified as plants, but that has changed! Fungi are a distinct group of organisms that include mushrooms, mold, and yeast, and are different from plants for two reasons: their cells walls are composed of chitin, and they don’t make their own food. Plants have cell walls composed of cellulose and use photosynthesis to make their own food.

Fungi are microscopic to macroscopic in size. As a matter of fact, the largest single living organism on Earth is the Humongous fungus (Armillaria ostoyae), which is nearly four-square miles in size (BBC, 2014).

Fungi are parasites which are found everywhere on the Earth. Not only do they live in air, water, and on land, but they live in and on plants and animals, including humans. Brown et al., (2012) estimated that at least 25% of the human population (1.9 billion people) have fungal infections of the skin, hair, and nails. Further, systemic fungal infections kill three times as many people than malaria does (Bongomin et al., 2017). The World Health Organization reported that malaria took the lives of 620,000 people worldwide in 2017, which would mean that systemic fungal infections caused up to 1,860,000 fatalities. Fungi leading to mortality rates ranging from 20% - 95% are cryptococcosis (Cryptococcus spp.) candidiasis (Candida spp.), pneumocystosis (Pneumocystis spp.), and aspergillosis (Aspergillus spp). 

Anti-fungal Drugs

Fungi are becoming ever more resistant to multiple drugs. Candida spp. and Aspergillus spp. are showing resistance to Azole anti-fungal drugs, and some Candida spp. (e.g. C. albans) are showing resistance to the Echinocandin class of anti-fungal drugs as well as to Amphotericin B – an antifungal medication used for very serious fungal infections (Lortholary et al., 2011; Alexander et al., 2013; Arendrup & Perlin, 2014). Not only are some of the most recognized and heavily prescribed anti-fungal medications occasionally ineffective, some of these medications are extremely exorbitant (ranging in price from $28,000 USD - $86,000 USD) – and are therefore limited to only those who are covered under health insurance or who can afford to pay out-of-pocket for them (Drgona et al., 2014). 

Is there a more affordable and effective way to combat fungal infections? It was reported that essential oils extracted from plants in the family Lamiaceae may be good candidates (Karpinski, 2020).

Essential Oils

Essential oils promote the breakdown of cell walls and cell membranes. Lipophilic (fat loving) compounds found in essential oils pass through these barriers and, by damaging structural molecules, make the cell permeable. When there is a change in permeability, the pH changes and cellular organelles get damaged. These same compounds also prevent the synthesis of fungal DNA, RNA, proteins and polysaccharides, and the production of fungal toxins (Burt, 2004; Helal et al., 2006; Rammanee et al., 2011; DeLiraMota et al., 2012; Hyldgaard et al., 2012; Wojtunik-Kulesza et al., 2019).

Lamiaceae (Labiatae)

The Lamiaceae family of plants encompass 236 genera and between 6900-7200 species. The majority of essential oil-bearing plants belong to this family, and they include, for example, the genera Lavandula, Salvia, Thymus, Ocimum and Origanum. The ten most common chemical constituents found in this family are: beta-caryophyllene, alpha-pinene, beta-pinene, 1,8 cineole, linalool, limonene, carvacrol, thymol, gama-terpinene, and para-cymene.

Scientific evidence has shown that these ten constituents exhibit significant anti-fungal activity (Yang et al., 1999; Kordali et al., 2008; Marei et al., 2012; Abbaszadeh et al., 2014; Dahham, 2015; Selestino et al., 2017; Bona et al., 2016; de Oliveira et al., 2017; Rivera-Yanez et al., 2017; de Macedo et al, 2018; Shi et al., 2019; Wang et al, 2019 - cited in Karpinski, 2020).

Some essential oils that contain these constituents, and which have been shown to have the strongest anti-fungal activity, include Hyssop (Hyssopus officinalis), True lavender (Lavandula angustifolia), Spanish lavender (L. stoechas) (Figure 1), Spearmint (Mentha spicata), Cornmint (M. suaveolens), Oregano (Origanum vulgare), Common sage (Salvia officinalis), and Vitex (Vitex agnus-castus). Please refer to Karpinski (2020) for a list of specific fungi these essential oils are effective against.

Figure 1. Spanish lavender (Lavandula stoechas)

Marjoram (Origanum majorana), Basil (Ocimum basilicum), and Thyme (Thymus vulgaris) also have anti-fungal activity, but their strength can vary depending on their chemical composition.

Future

There is ample in vitro evidence that shows that certain essential oils overcome drug-resistant fungi, and that they may be used alone or in conjunction with anti-fungal drugs to help inhibit external and internal fungal infections.  This alternative is also more cost effective, and readily available to those without health insurance or unable to afford medication.

Formula for lung infections caused by Aspergillus niger

Stock blend, 15 ml

• Marjoram (Origanum majorana) 100 drops
• Patchouli (Pogostemon cablin) 100 drops
• Spanish lavender (Lavandula stoechas) 50 drops
• Spearmint (Mentha spicata) 50 drops

Add 10 drops of stock blend to diffuser
Diffuse for 20 minutes on
Repeat four times a day 

Safety profile: Tisserand & Young, 2014
Mucous membrane irritation (low risk)
Do not use if pregnant or breastfeeding
Potentially neurotoxic if camphor exceeds 56.2% in (L. stoechas)

Have an aromatic day!

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References

• Alexander, B.D., Johnson, M.D., Pfeiffer, C.D. et al. (2013). Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin. Infect. Dis. 56, 1724–1732.
• Arendrup, M.C. & Perlin, D.S. (2014). Echinocandin resistance: An emerging clinical problem? Curr. Opin. Infect. Dis. 27, 484–492.
• BBC (2014). British Broadcasting System – The largest living thing on Earth is a humongous fungus. http://www.bbc.co.uk/earth/story/20141114-the-biggest-organism-in-the-world [Accessed May 2 2020].
• Bongomin, F., Gago, S., Oladele, R.O., et al. (2017). Global and multi-national prevalence of fungal diseases—estimate precision. J. Fungi 2017, 3, 57.
• Brown, G.D., Denning, D.W., Gow, N.A., et al. (2012). Hidden killers: Human fungal infections. Sci. Transl. Med. 2012, 4.
• Burt, S.(2004). Essential oils: Their antibacterial properties and potential applications in foods—A review. Int.J. Food Microbiol. 94, 223–253.
• De Lira Mota,K.S., de Oliveira Pereira,F. de Oliveira, W.A. et al (2012). Antifungal activity of Thymus vulgaris L. essential oil and its constituent phytochemicals against Rhizopus oryzae: Interaction with ergosterol. Molecules. 17, 14418–14433.
• Drgona, L., Khachatryan, A., Stephens, J., et al. (2014). Clinical and economic burden of invasive fungal diseases in Europe: Focus on pre-emptive and empirical treatment of Aspergillus and Candida species. Eur. J. Clin. Microbiol. Infect. Dis. 33, 7–21.
• Helal,G.A., Sarhan,M.M., AbuShahla,A.N.K. (2006). Effects of Cymbopogon citratus L. essential oil on the growth, lipid content and morphogenesis of Aspergillus niger ML2-strain. J. Basic Microbiol. 2006, 46, 456–469.
• Hyldgaard,M., Mygind,T., & Meyer, R.L.(2012). Essential oils in food preservation: Mode of action, synergies, and interactions with food matrix components. Front. Microbiol. 3, 1–24.
• Karpinski, T. (2020). Essential Oils of Lamiaceae Family Plants as Antifungals. Biomolecules, 10 (103) 1-35.
• Lortholary, O., Desnos-Ollivier, M., Sitbon, K., et al. (2020). Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: A prospective multicenter study involving 2,441 patients. Antimicrob. Agents Chemother. 2011, 55, 532–538.
• Rammanee,K. & Hongpattarakere,T. (2011). Effects of tropical citrus essential oils on growth, aflatoxin production, and ultrastructure alterations of Aspergillus flavus and Aspergillus parasiticus. Food Bioprocess Technol. 4, 1050–1059.
• Tisserand, R. & Young, R. (2014). Essential Oil Safety: A Guide for Healthcare Professionals (2^nd ed). Elsevier, London.
• Wojtunik-Kulesza,K.A., Kasprzak,K., Oniszczuk,T., et al. ( 2019). Natural monoterpenes: Much more than only a scent. Chem. Biodiv. 16, e19004.
• Photo by: By Hamachidori - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=4076172