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.

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: The Inuit diet” — a future part of this series). 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 1/3 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) (Figure 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

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

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 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 Figure 3 as a bond-line diagram.

Figure 3. Bond-line diagram of germacrone

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.

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)

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

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 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 1 cm and 6 cm in height (Figure 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

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 (Figure 5) which is decomposed in the human body to salicylic acid, a relative of acetylsalicylic acid (commonly called Aspirin™).

Figure 5.  Ball-and-stick representation of the salicin molecule¹⁹

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% of limonene²² (Figure 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.

Figure 6. Ball-and-stick representation of the limonene molecule²⁴

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 aboriginal 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), commonly called Rock Tripe (Figure 7),²⁶ According to Inuit knowledge, this: “… can be boiled and the tea is drunk by those suffering from tuberculosis.”²⁷ 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).

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

Student questions

1. Draw the condensed formula of germacrone from the bond-line diagram.
2. The active molecule found in the Dwarf Willow is salicin.  
   i.    Draw its condensed formula. 
   ii.   What functional groups does it contain?  
   iii.  Would you expect salicin to be water-soluble? Give your       reasoning.
3. Orange oil contains limonene.  
   i.    Why does the name have an -ene ending? 
   ii.    Draw its condensed formula.  
   iii.    Would you expect the molecule to be water soluble? Give your reasoning.
4. Many molecules of medicinal benefit, such as limonene, belong to the family of organic compounds called monoterpenes. Monoterpenes consist of two of this molecule, joined together.  
   i.    What is this molecule? 
   ii.    What is its common and systematic name?  
   iii.    Draw its condensed formula. 

References and footnotes

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

About the authors

Ms. Chaim Christiana Andersen, Inuk of the Nunatsiavummiut, is currently an undergraduate student in the Environmental Science (Chemistry) program at the Grenfell Campus of Memorial University, Corner Brook, NL. Dr. Geoff Rayner-Canham is Professor of Chemistry at the Grenfell Campus.