Chemistry of the Cure

FIGURE 1
Chaim (right) holding a pack of Labrador tea and Geoff (left) holding a ball-and-stick model of the active constituent, germacrone. Credit: Pamela Gill, Grenfell Campus, Memorial University

Before modern synthetic and analytical chemistry, every civilization and culture had to find cures or palliatives for illness and disease from the natural world. We do not know how physiologically active materials were identified, but it was presumably by a trial-and-error basis. In this article, we have chosen to focus upon a few Inuit remedies and show how their action can be linked in many cases to specific, active molecules. But first, we need to give some background.

The essentiality of Inuit remedies – a personal view by Chaim Andersen

Prior to resettlement, Inuit lived nomadic lives and moving with season changes and animal migration was crucial to survival. My ancestors lived in a world where their decisions always had to be certain and consequence would never yield. Wrong decisions or erroneous choices meant certain death. For Inuit, resilience and adaptation were – and still are – great strengths which we possess. Through Elders and experience, just like Inuit women have with uluit,¹ it quickly becomes second nature to have the knowledge and skills required to maintain a good quality of life. For us, there was no stable settled community and there were certainly no medical facilities, so traditional methods and medicines were the primary form of care.

For survival, Inuit had to be very healthy people with a varied diet containing all the essential nutrients, including vitamins and minerals (see “Living on the edge: Some chemistry of the Inuit diet” – article nine of this issue). Cautionary measures had to be taken to ensure that food sources would not in any way endanger their health, such as smelling a piece of fish for possible bacterial contamination. Until the arrival of European diseases, such as the Spanish Flu pandemic of 1918 (which killed about one third of the Labrador Inuit), bacterial infection and injuries were the major source of ill-health.

Inuit culture is one of sharing information and caring for each other, and it was women who had the responsibility of tending to an ill or injured person. Inuit women passed down from generation to generation, and between themselves, the knowledge of which medicinal plants can be used, what specific times of the year they should be harvested and what illness or injury they pertain to.²

In this article, we will focus on just two of the medicinal plants that Inuit have used for remedies: the Labrador tea plant and the Dwarf Willow tree. We will show that the use of these traditional medicinal sources has an underlying biochemical basis.

Labrador tea (Mamaittuqutik)

Though commonly called Labrador tea,³ in fact this member of the Rhododendron family is ubiquitous in northern climates around the world. There are, in fact, three different species: northern Labrador tea (Rhododendron tomentosum); bog Labrador tea (Rhododendron groenlandicum) (Fig. 2); and western Labrador tea (Rhododendron columbianum). Labrador tea is sometimes drunk as a herbal tea (tisane), which may not be such a good idea in view of some toxic components of the leaves: in particular, they contain variable concentrations of the poisonous cyclic alcohol, ledol.⁴

What is more interesting for this article is the employment of Labrador tea as an antibiotic.⁵ Elizabeth Green Solis, an Inuk of Nain, Nunatsiavut, recalled that, in about 1940, when she was a little girl: “I remember falling down and cutting my leg and my grandmother chewed Indian [Labrador] tea leaves to put on my wound. It didn’t even get infected.”⁶

FIGURE 2
Bog Labrador tea in flower (sp. Rhododendron groenlandicum)⁷

It is of note that the leaves are usually mixed with oil or fat. For example, the Inuit of Nunavik use it as: “A strong ointment … made by boiling the leaves and mixing them with a little clear fried seal oil and water.”⁸ Also, there are several references to making an ointment of Labrador tea with seal fat to treat eye disorders.⁹ Is there any evidence that Labrador tea really is an antibiotic? The key active compound in Labrador tea is germacrone. The molecule is shown in Fig. 3 as a bond-line diagram.

As can be seen from the figure, germacrone is essentially a poly-alkene with one ketone functional group (germacrone is chemically-classed as a terpene). Apart from the ketone, then, the molecule is non-polar and would therefore have very low solubility in water. However, in oil or fat, it would be expected to be highly soluble – hence the importance of seal oil or seal fat in making up the ointment.

FIGURE 3 
Bond-line diagram of germacrone. Credit: https://en.wikipedia.org/wiki/
Germacrone#/media/File:Germacrone_structure.svg

Other plant families contain germacrone. It is striking that germacrone-containing plants in Indonesia are also valued for their medicinal properties.¹⁰ There is also evidence of anti-viral properties of germacrone.¹¹ Finally, why does Labrador tea synthesize germacrone? It has been discovered that germacrone prevents Labrador tea from being eaten by snowshoe hares.¹²

Dwarf Willow (Amaallinaaq)

With the very short growing season, harsh climate and very few nutrients in the rock crevices, one response of plants in the Arctic is to become very much smaller.¹³ The willow tree is one such example. A member of the willow family grows as a tiny bush in the Arctic environment, between one cm and six cm in height (Fig. 4), and it is called the dwarf willow (Salix herbacea).¹⁴ The Inuit utilized the analgesic properties of this plant, and in a compendium of Inuit medicinal plants, it was reported that: “To ease the pain of a toothache … the peeled root of a dwarf willow is bitten on top of the sore tooth. This numbs the pain … ”.¹⁵

FIGURE 4 
Dwarf Willow with seed capsules. (sp. Salix herbacea)¹⁶

The analgesic properties of parts of the willow tree have been known for thousands of years in the West.¹⁷ Yet isolated in North America since the Ice Age, the Inuit must have gone through the same steps of experimentation independently in order to deduce its efficacy as a pain-killer. We now know that the pain-killing compound is salicin¹⁸ (Fig. 5) which is decomposed in the human body to salicylic acid, a relative of acetylsalicylic acid (commonly called Aspirin™).

Modern traditional remedies

As we have mentioned previously in this series, a living culture is one which changes and adapts, and Inuit philosophy fits this definition. For example, snowblindness (or more correctly, photokeratitis) is a common problem in the north, even though Inuit have always worn snow goggles when feasible. According to Wikipedia, there is no specific cure for this ailment.²⁰

The treatment adopted in recent times by Inuit of the Nunavimmiut is to squeeze the orange oil from orange peel/rind into the eye. As one Inuk commented: “Not truly traditional is it? But it works!”²¹ Is there medical evidence? Indeed there is!

Orange oil contains over 90 per cent of limonene²² (Fig. 6), a cyclo-alkene (also classed as a terpene). Limonene has been established as a potent anti-inflammatory²³ and almost certainly acts in this way as a treatment for snowblindness.

Commentary

For the Inuit living in such harsh lands, illness has not been an option. Every resource had to be investigated for its potential healing properties. In this article, we have included specific case-studies in which the active molecule is established by modern science and medicine. Are there useful pharmaceuticals yet to be identified in remedies used by indigenous peoples? Tulp and Bohlin consider that there are many novel, naturally-occurring molecules remaining to be discovered: “Nature always has been a valuable source of drugs and, despite the unprecedented opportunities afforded by medicinal chemistry, continues to deliver lead compounds.”²⁵

Some of these sources may be in the North. For example, another Inuit remedy is a black lichen (Umbilicaria esculenta), commonly called Rock Tripe (Fig. 7).²⁶According to Inuit knowledge, this: “… can be boiled and the tea is drunk by those suffering from tuberculosis.”²⁷

FIGURE 7 
Rock Tripe growing on a rock (with ice crystals). (sp. Umbilicaria esculenta)³⁰

Tuberculosis is still, today, a major health issue for the Inuit.²⁸ As some lichens are known to contain broad spectrum antibiotic compounds,²⁹ maybe the answer is growing on the Arctic rocks (especially considering Rock Tripe has been used since ancient times for medicinal purposes in China, Japan and Korea).

References and footnotes

1. Andersen, C.C.; Rayner-Canham, G. The Ulu: Chemistry and Inuit women’s culture. Chem 13 News, March 2019.
2. Projet sur la médecine traditionelle (Traditional [Inuit] Medicine Project) Interim Report; Institut culturel Avataq, 1983, p. i.
3. Wikipedia. Labrador tea. https://en.wikipedia.org/wiki/Labrador_tea.
4. Dampc, A.; Luczkiewicz, M. Labrador tea – the aromatic beverage and spice: a review of origin, processing and safety. Journal of the Science of Food and Agriculture 2015, 95, 1577-1583.
5. Black, P. et al. Seasonal variation of phenolic constituents and medicinal activities of Northern Labrador tea, Rhododendron tomentosum ssp. subarcticum, an Inuit and Cree First Nations traditional medicine. Planta Medica 2011, 77, 1655-1662.4.
6. Solis, E.G. I am an Eskimo. Them Days 1990, 16 (1), 35.
7. Wikipedia. Rhododendron groenlandicum. https:// en.wikipedia.org/wiki/Rhododendron_groenlandicum#/media/ File:Rhododendron_groenlandicum.jpg.
8. Ref. 2, p. 31.
9. Traditional Medicine. Labrador Tea (Mamaittuqutik). http://www. avataq.qc.ca/en/Nunavimmiuts/Traditional-Medicine/Medicinal- substances/Herbal-teas.
10. Diastuti, H. et al. Antibacterial Activity of Germacrane type Sesquiterpenes from curcuma heyneana Rhizomes. Indonesian Journal of Chemistry 2014, 14 (1), 32-36.
11. Liao, Q. et al. Germacrone inhibits early stages of influenza virus infection. Antiviral Research 2013, 100, 578-588.
12. Reichardt, P.B. et al. Germacrone defends Labrador tea from browsing by Snowshoe Hares. Journal of Chemical Ecology 1990, 16, 1961-1970.
13. Billings, W.D.; Mooney, H.A. The Ecology of Arctic and Alpine Plants. Biological Reviews 1968, 43, 481-529.
14. Wikipedia. Salix herbacea. https://en.wikipedia.org/wiki/Salix_ herbacea.
15. Ref. 2, p. 17.
16. Wikipedia. Salix herbacea. https://en.wikipedia.org/wiki/Salix_ herbacea#/media/File:Salix_herbacea_a3.jpg. Photo by Opioła Jerzy.
17. Mahdi, J.G. et al. The Historical Analysis of Aspirin Discovery, its Relation to the Willow Tree and antiproliferative and anticancer potential. Cell Proliferation 2006, 39 (2), 147-155.
18. Wikipedia. Salicin. https://en.wikipedia.org/wiki/Salicin.
19. Wikipedia. Ball-and-stick model of salicin molecule. https:// en.wikipedia.org/wiki/Salicin#/media/File:Salicin-from-xtal-1984- 3D-balls.png.
20. Wikipedia. Photokeratitis. https://en.wikipedia.org/wiki/ Photokeratitis.
21. Ref. 2, p. iii.
22. Wikipedia. Orange oil. https://en.wikipedia.org/wiki/Orange_oil.
23. Hirota, R. et al. Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka). Journal of Food Science 2010, 75 (3), H87-92.
24. Wikimedia Commons. File:Limonene-3D-balls.png. Commons. https://foundation.wikimedia.org/wiki/File:Limonene-3D-balls.png.
25. Tulp, M.; Bohlin, L. Unconventional natural sources for future drug discovery. Drug Discovery Today 2004, 9, 450-458.
26. Wikipedia. Rock Tripe. https://en.wikipedia.org/wiki/Rock_tripe.
27. Ref. 2, page 35.
28. Patterson, M.; Finn, S.; Barker, K. Addressing tuberculosis among Inuit in Canada. Canada Communicable Disease Report 2018, 44 (3/4), 82-85.
29. Shukla, V.; Joshi, G.P.; Rawat, M.S.M. Lichens as a potential natural source of bioactive compounds: a review. Phytochemistry Reviews 2010, 9, 303-314.
30. Wikipedia Commons. File:Umbilicaria sp.jpg. A species of Umbilicaria lichen growing on a rock in Nanortalik, Greenland. Author: Jens Buurgaard Nielsen. Date: December 2005. https:// commons.wikimedia.org/wiki/File:Umbilicaria_sp.jpg.

Publisher's note: This article is a reprint from the May 2019 issue of Chem 13 News.