Tree-sourced remedies for infectious diseases

WITHOUT vaccines, antibiotics and anti-viral drugs our ancestors were forced to rely on natural remedies to ward off infectious disease, or at least to alleviate the effects. Fast-forward hundreds of years and, despite huge advances in medicine, the world is once again without a vaccine or dedicated and clinically proven anti-viral drug for the coronavirus COVID-19. We now know the COVID-19 disease is caused by a sub-microscopic particle composed of RNA (ribonucleic acid) enveloped in a protein coat, whereas centuries ago viruses like COVID-19 and bacterial diseases such as bubonic plague would have been ascribed to the forces of evil.

As such, remedies used by early medical practitioners and alchemists were invariably based on strong-smelling plants including sweet-scented flowers or aromatic leaves and bark. So what are these natural remedies that have evolved over the centuries, with some subsequently contributing to modern medicine? Moreover, which ones are associated with trees? And how far has modern scientific research gone in demonstrating their antiviral properties?

Sweet smelling flowers of common elder were carried in posies to ward off the plague.

JUNIPER AND ELDER

Flowers of common elder (Sambucus nigra), with the muscat-like fragrance of an essential oil, were a key component of flower posies worn during medieval times to ward off the plague. And they still feature in that well-known nursery rhyme, “Ring a ring a roses, a pocket full of posies, atishoo, atishoo, we all fall down”.

Extracts of elder berries and/or elder flowers sold in modern health-food shops are said to help with the common cold and flu. More recently, Australian researchers have reported how phytochemicals extracted from elderberry juice are effective against the early stages of influenza, blocking key viral proteins responsible for both attachment and entry into the host cells, and in later stages of the influenza cycle when the cells have been infected by inhibiting virus particle propagation.

Common juniper (Juniperus communis), with its highly aromatic and earthy essential oil in the berries and twigs, has centuries-old credentials in fighting ‘evil’ diseases, including bubonic plague. As late as 1870, branches of juniper were burned inside hospitals in France during smallpox epidemics. Juniper berry oil contains a range of volatile monoterpene hydrocarbons including pinene, mycene, sabinene and limonene.

Juniperus communis has the distinction of having the largest geographical range of any woody plant species. It exists as a number of subspecies in a circumpolar distribution throughout the cool temperate northern hemisphere from the Arctic down to 30°N latitude, and right across North America, Europe and Asia. And wherever you look, from the Native Indians of North America to Ancient Greek and Roman civilisations and Chinese medicine, juniper has an unparalleled provenance in ancient medicine and folklore.

Common juniper berries, leaves and wood have an exceptionally long history stretching back centuries for use against infectious diseases like the plague, then believed to be caused by evil forces (picture copyright Andrew Gagg/Plantlife).

WILLOW PAVES THE WAY FOR ASPIRIN

Aspirin, the most widely used drug worldwide, was born in 1897, when German chemist Felix Hoffman synthesised the active chemical (acetylsalicylic acid –ASA) in the laboratory. Aspirin was patented in 1899, which set the scene for future use first as an antipyretic (reduces fever) and anti-inflammatory drug. It was subsequently used to prevent cardiovascular and cerebrovascular diseases via its anti-blood platelet properties. The story of aspirin continues today, with increasing evidence of chemo-preventive effect against certain cancers.

However, the story of aspirin dates back more than 3,500 years with its roots in willow, when this tree’s bark was used as a painkiller and antipyretic by the Sumerians and Egyptians and subsequently by the great physicians of Ancient Greece and Rome. Hippocrates, the Greek father of medicine, gave women a brew made from willow to ease the pains of childbirth in the fifth century. Had he but known it, Hippocrates had produced the aspirin we know today.

Indeed, the ‘sali’ component of the chemical’s name is testimony to the presence of a chemical called ‘salicin’, present in a wide range of willows – the Salix species. Salicin is not actually aspirin, but a precursor chemical which is converted into acetylsalicylic acid. The 19th-century chemists who finally isolated, synthesised and elucidated the mode of action of aspirin were clearly inspired by what was already known about salicin as a naturally occurring chemical in willow trees.

Communities across medieval Europe (including Britain) boiled up willow bark into a popular herbal remedy for fighting fever, but bark stripping of willows became punishable by law to protect the burgeoning wicker industry. At least three native British willow species, Salix alba (white willow), Salix petandra (bay willow) and Salix purpurea (purple osier), are known to contain salicin.

The South American Cinchona tree and source of quinine belongs to the Rubiaceae, a huge plant family of mainly evergreen trees which counts coffee (seen here) amongst its members.

CAMPHOR AND EUCALYPTUS

Countless trees are used as a source of traditional herbal medicines to fight all sorts of diseases, including respiratory complaints and their symptoms – to such an extent that you have to actually live in an overseas community to comprehend the wealth of local tree-sourced remedies around the world. However, some of these with centuries-old credentials are universally accepted, including classic tree-sourced remedies like camphor and Eucalyptus oil.

Camphor oil, with its multi-generational use as a pain-killer and for antitussive effects (preventing or relieving a cough), is derived from the bark of the camphor laurel (Cinnamomum camphora), a large evergreen tree native to China south of the Yangtze River, southern Japan, Korea and Vietnam.  As the common name suggests the cinnamon tree belongs to the laurel family (Lauraceae) a huge family of trees and shrubs including well-known species such as bay laurel and avocado. Camphor was traditionally produced by steam distillation of the bark to produce a white or transparent solid wax with a strong aromatic odour, valued since ancient times to fight disease including for use as a fumigant during the ‘Black Death’, the bubonic plague of Medieval times caused by the bacterium Yersinia pestis, transmitted to humans by rodents.

Laboratory synthesis of camphor was perfected in the first decade of the twentieth century. Contemporary focus is now on anti-viral properties with Russian researchers demonstrating activity against influenza viruses A and B by a camphor derivative called camphecene.

Unlike the many centuries-old uses of camphor, the medicinal benefits of eucalyptus oil were not realised until the last 200 years because the vast majority of eucalyptus tree species were confined to Australia, which was not ‘opened up’ until the 19th century. Be that as it may, the highly aromatic oil obtained by distillation of the leaves has since more than compensated in its contribution to medicine for a wide spectrum of benefits including relief of decongestion, pain and fever.

That said, the medicinal benefits of eucalyptus were being put to use long before the first European settlers arrived in Australia, by its native aboriginal peoples who used the so-called bush medicine by extracting eucalyptus oil from sap, leaves, bark and roots; by burning the leaves for inhalation; and by using the leaves and/or gum as a poultice. Native Australians used various species from the many hundreds of eucalyptus species which grow all over Australia, although today’s main source of eucalyptus oil is the Tasmanian blue gum (Eucalyptus globulus).

More recent research has focussed on anti-microbial properties, with natural oils in eucalyptus and another Australian native tree – the tea tree (Melaleuca alternifolia) – demonstrating antiviral activity.

Medicinal properties of eucalyptus were not widely known until 200 years ago when Australia was colonised by Europeans, although they were utilised by native Australian Aboriginal communities long before that. Red river gum (Eucalyptus camaldulensis) is one of the most widely distributed eucalyptus species in Australia.

TREE CHEMICALS AND COVID-19

So what’s the score so far for natural tree-sourced chemicals in the fight against COVID-19? The best description of the search is ‘feverish’, just like a key symptom of this disease. Bona fide scientific investigations are springing up around the world. Prominent at the moment is research around quinine, the world’s oldest anti-malarial drug. Quinine is sourced from certain species of native South American Cinchona tree species, all evergreens and members of the plant family Rubiaceae, which includes coffee (Coffea species).

Quinine was used to treat malaria long before the tree was given a scientific name – indeed, from as early as the 1600s when it was referred to as the ‘Jesuits’ bark’, ‘cardinal’s bark’ or ‘sacred bark’, these names stemming from first use in 1630 by Jesuit missionaries in South America, though legend suggests even earlier use by the native South American Indians.

Harvesting bark is a destructive process and must be done without killing the tree. One approach for Cinchona was to cut the tree, but this and girdling proved equally destructive and unsustainable.  Instead, small strips were cut and various techniques such as ‘mossing’ (the application of moss to the cut areas) were used to allow the tree bark to heal. Other approaches involved coppicing and use of the coppice rods, which were cut and stripped of bark.

Research has demonstrated anti-viral activity by phytochemicals contained in elder berries.

Before 1820, bark taken from the Cinchona tree was dried into strips called quills, ground to a fine powder and then mixed into a liquid (commonly wine) before being drunk. In 1820, pure quinine was extracted from the bark, isolated and named by Pierre Joseph Pelletier and Joseph Caventou in France. Purified quinine then replaced the bark as the standard treatment for malaria and remained so for 100 years until replaced by synthetically produced quinine-related drugs like chloroquine.

This generic anti-malarial (chloroquine) is claimed to alleviate the symptoms of COVID-19, with promising results reported from China and France. It has even caught the interest of Donald Trump, but communities around the world appear to be ahead of the game, with reports that online pharmacies have already run out of supplies, sadly with some serious consequences due to side effects and poisoning from over-dosing.

Other promising reports relate to already established anti-viral drugs including Remdesvir, developed to combat Ebola; and Oseltamivir, sold under the brand name Tamiflu, an anti-viral medication used against influenza A and B viruses and widely deployed against the H5N1 avian influenza (bird flu) pandemic in Asia some 15 years ago. The starting point for synthesis of Oseltamivir was shikimic acid, extracted from a tree called Chinese star anise (Illicium verum), a medium-sized evergreen native to north-east Vietnam and south-west China.

Last but not least is recent excitement around vitamin C, long-claimed to fight off the common cold when taken in time and in a sufficiently high dose. Indeed, I remember my lecturer Dr Ashton in Agricultural Biochemistry at University College Wales, Aberystwyth in 1965 swearing blind by a dose of vitamin C when you felt the first effects of a common cold.

There are innumerable tree- and shrub-related sources of vitamin C around the world, most known only to local communities in the regions where they grow. Brits would traditionally reach for rosehips, blackcurrants, lemon or lime, but there are exotic trees and shrubs used in UK forestry or grown ornamentally for various reasons which offer excellent sources of vitamin C. One such species is the autumn olive (Elaeagnus umbellata), well established as a nurse species for walnut (Juglans) but bearing berries rich in vitamin C. However, it’s not a source I would favour. Autumn olive berries are apparently edible, but there are many red-berry bearing shrubs and trees that resemble this species with berries which are not only inedible but poisonous.

Autumn olive is well established as a nurse species for walnut but also has a very high concentration of Vitamin C in the ripe berries (picture courtesy Dr Jo Clark, the Earth Trust).

INHERENT DANGERS OF JUMPING THE GUN

Drugs invariably have side effects and it is easy to overdose even on nominally beneficial substances like vitamin C, so jumping the gun is clearly a real and present danger, especially with the mass media pumping out all sorts of fake news about COVID-19. Tragedies are already occurring, with people around the world desperately worried and prepared to do anything to avoid the consequences.

Reports from India describe serious illness and death from overdosing on the anti-malarial drug hydroxychloroquine in an effort to avoid the worst of COVID-19. And there have been hundreds of deaths across Iran from methanol poisoning following false reports that methanol (methylated spirits) provides a cure. Methanol is also called wood alcohol because it was originally produced by the distillation of wood. Pure methanol was first isolated in 1661 by Robert Boyle, who produced the chemical compound via distillation of boxwood (Buxus).

USE AND ABUSE OF NATURE

There is an increasing school of thought that COVID-19 is a consequence of abuse of the natural order of things. This is not the first time that traditional Far East Asian wet meat markets (at which intensively farmed domestic and wild species of animal are slaughtered on the spot and sold to customers or sold live to be taken home and slaughtered) have themselves been the source of a pandemic zoonosis. A zoonosis is a disease of animals which can be passed to humans who will have no tolerance or resistance. As such, it is entirely fitting that other components of the natural order – in the form of specific trees and shrubs – should provide prevention or a cure.

However, special properties which allow these trees to be used to fight human disease may not prevent the trees themselves from succumbing to disease. Juniperus communis (common juniper) appears well on the way to extinction in the UK at the hands of an exotic fungus-like pathogen called Phytophthora austrocedri.

And there is an additional word of warning about the dangers of introducing exotic trees and shrubs which have medicinal properties. Camphor laurel, introduced into Australia in 1822, is now considered a noxious weed in Queensland, while autumn olive, introduced into the United States in 1930, is now highly invasive in a number of states, from New Hampshire to Wisconsin.

REFERENCES:

Garshinina, A.V., Tretiak, T.S. et al (2015) ‘Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo’. Antiviral Research Volume 120, August 2015, pages 126-133. https://doi.org/10.1016/j.antiviral.2015.06.004

Montinari, M.R., Minelli, S. and De Caterina, R. (2019) ‘The first 3500 years of asprin history from its roots – A concise summary’. Vascular Pharmacology 113:1-8. doi: 10.1016/j.vph.2018.10.008.

Torabian G., Valtchev P., Adil, Q and Dehghani, F. (2019) ‘Anti-influenza activity of elderberry (Sambucus nigra) (2019)’. Journal of Functional Foods, 54: 353 DOI: 10.1016/j.jff.2019.01.031

Usachev, E.V., Pyankov, O.V., Usacheva, O.V. and Agranovski, I.E. (2013) ‘Antiviral activity of tea tree and eucalyptus oil aerosol and vapour’. Journal of Aerosol Science 59: 22-30. https://doi.org/10.1016/j.jaerosci.2013.01.004.

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