Kava. No worries?

“When the mixture is not too strong, the subject attains a state of happy unconcern, well-being and contentment, free of physical and psycological excitement. At the beginning conversation comes in a gentle, easy flow and hearing and sight are honed, becoming able to perceive subtle shades of sound and vision. Kava soothes temperaments.” – Louis Lewin 1927

Via Cook Island Biodiversity Database – http://cookislands.bishopmuseum.org

Another herb story that exemplifies the complex often difficult path that traditional medicines travel in the modern world. Only some of which relates to the many and varied sciences that contribute to our understanding and recognition of them.

In this case a herb closer to home for me, the South Pacific pepper Piper methysticum, aka Kava or Awa.

A widespread and culturally significant plant consumed regularly by Pacific island people since well before European exploration and colonisation. This unique herb has however struggled for recognition globally since case reports of liver disease arose in Europe in the late 90’s and a rapid banning of it for human consumption in many developed countries has occurred during the early to mid 2000’s. Despite a rash of research and speculation on the causes and risks it is still unclear how many were really affected and by what, with numerous cases of concomitant use of liver toxins including pharmaceuticals and alcohol. However ongoing research continues to point towards some distinctly beneficial actions of Kava. Perhaps ironically in current circumstances, mostly in regard to the treatment of anxiety.

The genus Piper seems so distinctive, characteristic and yet minutely varied in detail from species to species. Found throughout the lowland tropical and subtropical rainforest lands of Asia, Africa, the Americas, Australia and W Pacific, there’s well over 1000 species recognised and it seems likely a few more that are yet to be resolved. The most commonly known product of these vines and shrubs is the fruit we call black pepper, Piper nigrum. With its own significance and importance in the history of western Europe since classical times. It was once worth almost the same as gold, today it is a cheap ubiquitous condiment on tables across the world.

Interestingly enough, it seems that P. methysticum is not one of those currently accepted names. In botanical speak its taxonomy and name is currently under review. Which is often the case with many of the more interesting and long cultivated plants that are of significant cultural interest to humans. It is not always easy to clearly delineate the species, their origin or relationships of different varieties or cultivars. This certainly seems to be the case with Kava, which cannot reproduce sexually and yet is found across Pacific islands as a bunch of distinctive cultivars and chemotypes. It seems most likely to be some sort of hybrid or sterile cultivar of P. wichmanii, which is found more in Papua New Guinea (the western and coastal or island provinces), the Solomon Islands and parts of Vanuatu. Only these two plants have been found to contain the active kavalactones. Though P. methysticum, the sterile cultivar, was ‘discovered’ and named by European botanists before P. wichmanii, the fertile wild type, creating some confusion that it seems is still unresolved.

Vanuatu is generally regarded as having the greatest range of Kava cultivars and is a likely epicentre of its distribution across the Pacific, making it as far as the Hawaiian islands before any European contact. It remains a major crop in Vanuatu, a significant cultural and economic plant. Though due to fears, the market for Kava in the UK and many other European countries dried up after bans were imposed in the early 2000’s. Kava seems to continue to be one of their largest agricultural crops though the government claims a 25% drop in export volume and significant reduction in markets from 2000 to 2010, primarily due to the bans imposed in the EU and elsewhere, including a ban on general public sale Australia in 2007.

It remains unclear what the issue really was with reports of liver damage and acute liver failure, with research focussing on type of extract solvent, part of the plant (roots or stems and leaves), concurrent alcohol or other drug use (prescription or otherwise), genetic susceptibility, metabolic polymorphism, overdosage etc. None of major constituents (kavalactones) or other reasons given above have been proven to induce hepatotoxicity. The age-old issue of poor quality and mouldy plant material containing aflatoxins appears a likely possibility not only for Kava, but is a risk for any poorly dried or stored plant materials including many human and animal plant foods. Aflatoxins are known to cause liver failure and in the longer term liver cancers.

Australia however also has a significant Pacific islander population and closer contact with the region and particularly countries such as New Zealand with a very large islander population. So Kava had been readily available and has been recognised as a culturally important product, a total ban on possession and use is unlikely to be enforceable here. There are ongoing campaigns from within some islander communities against the bans and limitations on Kava importation and use in Australia. It is not completely banned, individual importation of up to 2 kgs and personal use is legal, ostensibly for cultural reasons, however commercial or communal importation and social use or sharing is in effect illegal. The basis of islander Kava culture is in practice being repressed.

To a large extent the whole notion of legitimate social and cultural use of any plant drugs is still something that western contemporary societies can not tolerate or examine in any sensible way, despite it being a widespread phenomena in pretty much every human culture that has ever existed. This seems particularly so in contemporary Australia. Despite the often heard local idiom, no worries mate. When it comes to personal or social use of any ‘drug’ plants, some authorities are very worried and anxious to stop it.

In the case of Kava the campaign against it stems back to christian missionaries, as was the case for many culturally important plants around the world during early periods of European colonisation.

Kava Licence sign from Northern Territory, Australia.

There has been some heated debate and controls tried on Kava in Aboriginal communities in northern Australia. Where the ravages of land and cultural dispossession, historical marginalisation, poverty and alcohol are also elements of the situation. It has been a ‘controversial’ debate that continues. Some communities developed a licencing system for Kava and its use grew during the 1990’s and 2000’s until the change in importation laws in 2007. It seems unclear how widely used or available Kava is currently in those communities.

What research was done on Aboriginal Kava use has almost entirely focussed on speculation of, mostly unproven, physical harms. Which even if they are present are insignificant compared to the physical damage from alcohol and particularly the violence stemming from its use. Same for the social harms, although it seems acknowledged even by detractors that Kava does actually reduce domestic and community violence levels.

Kava calms people rather than creating a drunken violent stupor.

It is no longer available legally for general consumption, but a black market developed during previous local bans. It remains unclear if this will simply increase the use and abuse of alcohol or other more destructive drugs. Even after research on the Aboriginal communities using Kava, in a more traditional manner as water extracts, there has been no reports identifying it as a cause of the liver failure in these communities, despite many other factors increasing their risks.

That was supposed to be just some background and only really scratches the surface of the complex Kava story so far.

For a detailed appraisal of the ethnobotany of Kava there’s no better book than Kava The Pacific Elixir by Vincent Lebot, Mark Merlin and Lamont Lindstrom. It was published in 1997 before the recent anxiety and bans imposed on Kava.

The last Cochrane review of Kava for anxiety was done in 2007, even then it was noted that there appeared to have never been a case of hepatotoxicity or severe adverse events in any clinical trials available. Which remains the case as far as I can see.

“The meta-analysis of seven trials suggests a significant treatment effect for the total score on the Hamilton Anxiety Scale in favour of kava extract.“

In the same year a World Health Organisation sponsored report (Assessment of the Risk of Hepatotoxicity With Kava Products) suggests there is still no current understanding of what might be a cause of hepatotoxicity, with insufficient evidence available to justify the bans on its use in some countries. More recent reviews (paywall) and commentary have further called for considering an end to the ban on Kava due to lack of evidence.

Of more recent interest has been a randomised controlled trial of Kava for anxiety in Australia. Where preparations derived of aqueous extracts with no more than 250mg kavalactones /day maximum dose are still available for use or prescription by herbalists and health practitioners. Due to Kava bans or warnings, clinical research has virtually stopped in many European countries and north America.

Published in 2009 was KADSS (paywall), the Kava Anxiety Depression Spectrum Study. They measured scores for both anxiety and depression using standardised scales in a crossover trial with groups receiving placebo then kava or kava then placebo respectively during the study. There’s no single standard pharmaceutical therapy for anxiety but antidepressants have often been applied.

In this study Kava not only significantly reduced the anxiety score of participants, it also significantly improved their concurrent depressive symptoms. Again without significant adverse events. The only other research they could cite in regard to Kava and depression was a report on a Kava extract improving state cheerfulness, according to the State-Trait Cheerfulness Inventory, apparently.

Despite a lack of clear evidence justifying a ban on Kava, there has been little movement from UK and other authorities to even consider the research, or centuries of widespread use amongst Pacific Islanders, in regard to restrictions on Kava trade. Traditional use of aqueous extracts exceeds the ‘therapeutic dose’ used in clinical trials by a significant margin.

Kava cultivation – via Wikicommons – by Forest & Kim Starr – http://commons.wikimedia.org/  Piper_methysticum.jpg

Yet another interesting and intriguing herb, discovered by humans in pre-historical times, carried and cultivated by people as they explored their world. With a range of unique pharmacological actions that seem more useful than ever in our fast paced industrialised world of momentous changes. Which, despite our pretences to sophistication, we really don’t understand or know how to handle. So we ban it, hope it will go away?

Meanwhile the largest single cause of iatrogenic liver failure in humans is available to the general public as an over the counter medicine around most of the world, acetaminophen or paracetamol (Ibuprofen, Tylenol etc). Which is responsible for hundreds if not thousands of deaths and even more injuries due to liver trauma every year.

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A whole month of posts in one this time. There’s been an enormous amount of research, reports and debate over this herb recently, more than I figured when I started this post. I’m sure we’ll hear more.

Here Be Dragons ~ Blood

Dragons or Dinosaurs. The notion of large dangerous scaly creatures that will either crush or burn and eat us, or confer strength and immortality, seems a fairly common element of the human psyche.

Though even when people sailed or wandered off the edge of the world, real dragons have unfortunately been seemingly hard to come across.

Which of course didn’t stop people identifying the dark red resin that exudes from the trunk of some ancient looking trees, as Dragon’s Blood. Nor did it stop them calling the red resin exuded by other trees the same thing too.

via http://www.alte-landkarten.de/

The Socotran Dragon’s Blood specimens in the garden alongside the Aloes I’ve been watching flower, piqued my interest in these plants again. Despite a range of blogs and commentary (pdf) already out there, I’ll attempt to string together a few noteworthy points and links to sites of interest.

The oldest known from classical times was the Dragon’s Blood tree of Socotra (or Zocotra) in the Arabian sea. Obtained from the Socotran endemic species Dracaena cinnabari. Also known as Indian Cinnibar in classical times it rates a mention in the 1st century tour and trade guide to the Red and Arabian Sea coast with the wonderful title of The Periplus of the Erythrean Sea. Along with Frankincense as an article of trade on the island they called Dioscorida and we now call Socotra. Some articles cite the mythology of these trees arising from the blood of Ladon the Dragon (Draco Hesepros) who was slayed, or perhaps not. While trying to protect the Golden Apple tree in the Garden of the Hesperides from Herakles (Hercules) who was undertaking his 11^th task, to steal some golden apples.

It is a striking tree in what is the globally unique flora and landscape of Socotra. A remnant of the flora that apparently occured across northern Africa before the drier current times.

Dracaena cinnabari forest Socotra – via Postimage

The deep red resin that exudes from wounds on the trunk had been utilised locally and across the ancient world for medicine, dyeing and as a varnish ingredient. It is rarely used for medicine now, aside perhaps from the local folk traditions.

Though there are bigger problems for the trees these days. Whilst it seems historical demands and over harvesting contributed to a decline in production and increase in adulteration or substitution with other resins. Now broader human driven change in land use, grazing and climate change threaten a range of Socotra’s unique plants.

Dracaena cochinchinensis – via eFlora of China

In the early 15^th century a related species was found on the Canary islands, Dracaena draco, much later found also in Morocco. This was utilised as a primary source of resin too. In China, Dragon’s Blood (Sanguis Draconis) was also being used in medicine since at least the 7^th century, where it was also once called Unicorn Blood apparently. The local species from southern China, Vietnam and Cambodia, D. cochinchinensis, being tapped for the resin to the point it is also now vulnerable.

Overall it seems that all three of the tree type species are now vulnerable in their natural habitats. D. draco of the Canary Islands reduced to hundreds of individuals and the Socotran D. cinnibari populations diminishing in size and vigour over the centuries. D. cochincochinensis is listed as vulnerable in the Chinese flora as well.

In a world of seven billion plus people it is perhaps thankful that demand for this particular Dragon’s Blood seems at a historical low. It is perhaps also thankful that such unique and hardy trees have at least found themselves cultivated and appreciated all over the world, notwithstanding the pressing need to protect their natural habitats. D. cinnibari is a fairly common ornamental tree in Australia. D. draco is also in cultivation but I don’t know the status of the Asian species.

Dracaena cinnabari in the garden. They tend to grow tall and straight for a bit here and flower sometimes within 10 years. This one has regular inrease/decrease in stem girth, apparently due to periods of different rainfall. Nearly 5 m tall.

Wound in trunk of D. cinnabari showing some red resin

It seems one of the most common other Dragon’s Blood was the red resin obtained from the fruit of the Asian rattan palm Daemonorops draco. This one seems to be the most commonly traded resin these days around the world.

Daemonorops draco – via Wikipedia

Although this resin might look similar to Dracaena resins, they seems to have some different constituents and pharmacology. The Dracaena resins contain tannins, flavonoids and other constituents that have an overall astringent effect. Stopping bleeding and drying wounds and ulcers, with anti-microbial effects it was also traditionally used for treatment of diarrhoea and gastrointestinal illness. The Daemonorops resin contains some similar constituents such as flavonoids with sesquiterpenes that have anti-microbial effects, but limited previous research (pdf) suggests that it also might have an anticoagulant effect.

As is the case for many natural products there is actually quite little recent detailed research on these resins despite the advent of modern analytical methods. This one also appears to have enjoyed widespread use locally for centuries, then been traded globally. This seems the most likely source of hard red resins being marketed as Dragon’s Blood these days, including for use in Chinese medicines due to the vulnerable status of D. cochinchinensis.

Anyone who arrives here looking for Dragon’s Blood might also have been looking for another one, Sangre de Drago. This time it’s South American and generally comes as a liquid rather than tears or lumps of resin. From an altogether unrelated tree of the diverse genus Croton, in particular Croton lechleri. This one has only recently been widely known and available outside Amazonia. Despite generally being a liquid, more a latex really, the high levels of tannins make it a strong astringent which was widely used like the Dracaena resin to stop bleeding and dry ulcers or wounds, treat diarrhoea and gastrointestinal illness. The real stuff in my experience turns to a pale lather when rubbed on the skin or gums. Forming what some describe as a skin over wounds once it stops bleeding. There a bit more recent research on this one and some of the unique anti-microbial and wound healing constituents in it.

There are a few other plants producing red latex or resin that have variously been called or used as substitute for Dragon’s Blood, including apparently the kino from some Eucalyptus. Which was used for similar purposes in the local area for stopping bleeding, treating wounds, ulcers, diarrhoea and gastrointestinal diseases as well. The Leguminous tree Pterocarpus officinalis has also been the source of a resin and is also called Dragon’s Blood tree.

Like so many things botanical and human, it’s never quite as straightforward as you’d think.

No doubt there’s many other plants that produce blood-red resins as well. Resins seem to have been something that humans have had an interest in all over the world, for medicine, dyes and binding, though they are rarely more than a curiosity or incense in the modern world. They are a unique natural product that were formerly vital elements of human cultures.

D. cinnabari, Socotra – via Wikicommons

Further reading

Dragon’s blood: Botany, chemistry and therapeutic uses, Journal of Ethnopharmacology 115 (2008) 361–380  (pdf)

Dragons Blood, The Horticulturalist (2002)  (pdf)

New herb, an old story?

Fagonia cretica (credit Llez via WikiCommons)

It’s a simple line that seems likely to be interpreted in myriad ways and not be the last word.

“Cup of Herbal Tea Could Help Fight Breast Cancer”

Or more specifically

“An Aqueous Extract of Fagonia cretica Induces DNA Damage, Cell Cycle Arrest and Apoptosis in Breast Cancer Cells via FOXO3a and p53 Expression” (open access)

Sometimes in the human study of nature, reporting of scientific experiments can trigger a range of reactions, from wonder and curiosity to playing on deeply held hopes and fears. In the area of medicine and disease particularly so.

This newly reported research was a herb I’d not heard of before, or at least never payed any attention to. There’s more than a life time of plants in the world to ponder and continue to learn about and it does grow on the other side of the world from me. Perhaps some readers are more familiar with it.

The back story on this herb Fagonia however, when I dug a little deeper, echoed many a herb story the world has seen before. Various species of Fagonia seem to be fairly widespread and common plants across semi-arid northern Africa and Southern Europe to Sth central Asia. Linneaus however was apparently able to cultivate some F. cretica in Sweden to add to his collection, which anyone can now see here.

Fagonia cretica – from “The Botanical Magazine; Or, Flower-Garden Displayed”, by William Curtis, 1794

As for many traditional herbal medicines it seems to have been almost completely off the scientific research radar for the most part of the last century, with a more recent flurry of papers such as the one above. Though evidently it is a popular herb for largely impoverished and illiterate or poorly educated people in the area of its occurrence, in this case Pakistan. Where it seems a favoured remedy for gastrointestinal diseases according to this ethnobotanical survey (pdf).

Like so many stories botanical however, there also seems some complexity and taxonomic confusion over which Fagonia species was used or being referred to in different places and these different studies. Does it make any difference in regard to its likely effectiveness as a medicine? Maybe.

Fagonia is a genus of seemingly tough herbs from the Zygophyllaceae with a disjunct distribution in arid to semi-arid regions of the west American coast and right across northern Africa, the Mediterranean islands, Middle East, Horn of Africa and Persian Gulf countries to the NW areas of India and south central Asia. There is reference to F. cretica in the papers above and others, but the Pakistan Flora tells us that this species doesn’t actually grow there. Apparently there has been some confusion in the past but F. cretica is limited to African and the Mediterranean and Middle Eastern regions. So the flora suggests that references to F. cretica from the sub-continent region really refer to F. indica or particularly its variety schweinfurthii with trifoliate leaves like F. cretica.

Fagonia indica var. schweinfurthii – via eFlora of Pakistan

There are now very recent papers reporting extracts from both of these species as being active against cancer cells, the one above and this one – “A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells”.

There are a few other papers on the constituents of Fagonia and it seems there could be a range of different saponins produced from different species or locations, with either steroidal or triterpene glycosides. This class of plant constituent often occurs as a very complex mix and in this case there might be variation in the profiles even within individual species.

Plants, or semi-synthetic derivatives of their constituents, have provided many of the currently used anti-cancer drugs (vincristine, vinblastine, paclitaxel and others), but it is rarely a straightforward situation. Aside from the potential complexity of the chemistry and biological action involved, that will likely take many years of varied experiments to identify and even more to understand. The path from traditional herb to pharmaceutical can be complex in the cultural, economic and ecological spheres as well.

The conventional pharma model would see further isolation of the ‘active’ constituent, in this case it seems unlikely to be cheaply and easily made by synthesis. Then packaging as a pharmaceutical. After many years and millions of dollars of research and trials, a treatment just may come out of it. Though given the way of pharmaceutical interests, all of this seems unlikely to develop without someone getting some sort of IP interest in it somehow. This is also likely to ignore any other constituents and traditional preparations, aiming for a purified extract, or synthetically altered derivative.

The populations who know and use the herb, perhaps originally because they have few other affordable or effective options, are not likely to see much benefit from any development as a pharmaceutical. Or much recognition of their prior art in having knowledge of the herb as a medicine. Fagonia seems cosmopolitan and distributed across a range of countries and cultures, there seems no natural monopoly for anyone in it. There have been some cases of other plants from the sub-continent being the subject of court cases over patenting for medicines or foods. The development of the Indian Traditional Knowledge Digital Library was to counter patents based on traditional use by publishing the prior herbal knowledge online.  Fagonia gets a mention there in a dozen or so traditional formulations there.

Meanwhile anyone directly or indirectly confronted with a cancer diagnosis is obviously wondering if it could prove an answer for them or their loved ones. It is likely there will be some interest and perhaps some trying to capitalise on that. Sudden rushes of interest can drive demand before true knowledge and understanding, even threatening rare species.

At least in this case it seems Fagonia is not rare, growing across a wide area of otherwise arid to semi-arid land it also seems less likely to be as threatened by human activities as many other herbs. If anything it might be one those tough adaptive plants that has or will expand from human disturbance, particularly with increased aridity.

A long history of human use suggests traditional preparations (tea) are reasonably safe.  Though issues around risks associated with identification, natural variation, adulteration or contamination for the average urbanised person wanting to get hold of some for themselves are likely to pass most people by. In terms of understanding these issues in Fagonia, there seems quite some way to go. Though I wouldn’t be surprised if those otherwise older illiterate or uneducated people of Pakistan and elsewhere actually had a pretty thorough working knowledge and experience of this plant in their local area.

The path from folk medicine to pharmaceutical is often a long and rocky one. Though this is also where the majority of modern drugs have come from directly, or by derivation. For many in the world though, the traditional use and availability of herbal medicines as a component of their local flora has been or is a necessary aspect of survival.

We’ll see if anything further develops.

Fagonia cretica (credit Llez via WikiCommons)

Aloes

Aloe ferox

The orange-red inflorescence of an Aloe ferox.

The recent prolific mid-winter flowering in a range of Aloe species had piqued my interest again in this mostly African genus of plants.

There’s been at least half a dozen species flowering and after a good soaking this year most have been throwing out plenty of flowers in response to just a bit of mid-winter sun.

Aloe arborescens

Aloe sp.

Aloe sp.

Aloe ferox under a Dragons Blood tree (Dracaena cinnabari)

Aloe vera

Aloe sp.

 

The popularity of Aloe vera gel for skin and digestive health and repair has grown around the world, though it seems many people don’t really know where the plant originates and how large the Aloe genus is. There are 516 species recognised currently according to The Plant List.

Aloe ferox is one the primary sources of an old medicine, Aloes, often called Cape Aloes. The dried yellow exudate from just beneath the skin of the leaf. The golden orange-brown colour being due to the characteristic presence of the anthraquinones known as aloins (aloe-emodin, barbaloin and isobarbaloin), and this thin layer of latex producing cells just below the skin is a characteristic of all Aloes.

Aloe ferox – cut leaf with orange brown latex

Aloe ferox – leaf with anthraquinone bearing latex cells

Anthraquinones are quite well-known and found in various forms in a range of other long utilised herbs, such as rhubarbs (Rheum), docks (Rumex) and knotroots (Polygonum, Fallopia), Cassia and Senna, buckthorns (Rhamnus) and madders (Rubia). Mostly they are from a few specific and smaller families. The main action of anthraquinones in humans, long known across many cultures, is as a laxative or in higher doses as a purgative.

Cape Aloes once held a significant place as a herbal medicine, though it is less known, used or available in the herb trade of contemporary times. There does still seem to be some small industry mostly in Africa. Once widely used in low doses in many patent and over the counter remedies, or in bitter tonics, it has fallen largely out of use. The FDA withdrew its status as GRAS (generally regarded as safe) in the US in 2002 after no product sponsors came forward to provide supporting evidence for a review, or perhaps no sponsors had any significant products containing it at the time. It seems that the less concentrated and potent Senna or Cassia products are readily available and preferable agents for most these days.

Aloe socotrina – another historical source of Aloes latex

The anthraquinones themselves, from Aloe and other plants, continue to be investigated for a range of pharmacological activities aside from their laxative action. With anti-inflammatory, anti-fungal, anti-cancer and even anti-malarial research using anthraquinones. Of course with such strongly active compounds there are some issues when it comes to chronic consumption, though this applies to Senna and other anthraquinone based laxatives too. We don’t absorb them very well into our circulation generally, they act directly on the large bowel for the laxative action by decreasing water and electrolyte reabsorption.

The strength of some anthraquinones as pigments also saw them utilised in dyeing of materials. With the anthraquinone alizarin from madder (Rubia tinctorum) the first chemically synthesised dye, turkey red, that was widely available.

Aloes were considered members of that diverse tribe of plants the Liliaceae, the Lilies. Though it’s not really until they flower that many would see the relationship with what most would think of as Lilies.

The diversity of the Liliaceae seems to have all been a bit of taxonomic nightmare for a while, so it was interesting to see how a few different sources classified Aloe even now. For those readers with little knowledge of the complexities of plant taxonomy, the confusion probably starts here.

I found a few of the sources I would regard as the best that at first glance had a slightly different take on the taxonomy of Aloes.

The Plant List places them in the Family Asparagaceae, alongside a large bunch of varied plants from Asparagus and Aspidistra to the Butchers Broom, Ruscus.

Whilst African sources (eg PlantzAfrica and Flora of Mozambique) seem to still have them in a family all their own, the Aloeaceae.

Xanthorrhoea australis– via Wikipedia

A review in the Annals of Botany (pdf) and Angiosperm Phylogeny  site has them in the Order Asparagles, family Xanthorrhoeaceae, sub-family Asphodeloideae. Which is kind of interesting from an Australian perspective given the widespread endemic occurrence of Xanthorrhoea, grass trees, here. Not an immediately obvious relationship to most I’m sure. It is around a 180 million years since Africa and Australia were connected, via Antartica, as part of the Gwondana supercontinent. Though phylogenetic studies suggest that Xanthorrhoeaceae is only from 50-90 millions years old, which is evidently a long time after Africa and Australia were separated. The Aloeaceae and Asphodelaceae are evidently synonyms for some members of the this family.

It’s easier to see a relationship with our local Bulbine lillies (Bulbine bulbosa and others) that are considered members of the sub-family Asphodelaceae as well.

Bulbine bulbosa

The type species of the Asphodelaceae, Asphodelus, is named after the mythical meadows of Asphodel a kind of middle of the road domain of the underworld where the dead ate flowers, apparently for lack of much else to do. However the brilliant show from the Aloes seems more appropriate for the everlasting reverie of the Elysian fields. Perhaps that is how our local honey eaters (birds) have felt at least, with the winter long supply of nectar from these colourful Aloe flowers that they’ve been enjoying.

Aloe ferox

Further reading:

Chen, Van Wyk, Vermaak and Viljoen, Cape Aloes – A review of the Phytochemistry, Pharmacology and Commercialisation of Aloe Ferox, Phytochemistry Letters, vol 5: 1-12, 2012

How old is herbal medicine?

For the most part, herbal medicine traditions identify themselves from the time of the oldest extant texts in their cultural tradition, Hippocrates, Shennong etc.

Often enough the first texts of any recognisable form in many cultures were herbal texts, encompassing the broad natural sciences and concepts of human disease from the time.

It seems pretty clear to me that use of plants for medicine is not only a virtually universal human phenomena, as an oral traditional before written language, but also an aspect of life for many animals.

So how far back could we find evidence for herbal medicine in humans or hominids? Assuming we ignore the documented use of plants by our brethren apes for now.

Shanidar cave, Erbil Govenorate, Iraq

Some more recent research adds to the story started with the discovery of the 60,000 year old Neanderthal ‘flower burial’ in the late 1950’s. The Shanidar IV skeleton was discovered buried deep inside the Shanidar cave of modern-day northern Iraq. In this unique burial a skeleton was found with a plume of pollen and woody material evidently from a ‘bouquet’ of herb flowers strewn over and around the body at burial.

Many of those species identified at the time were still to be found in the area and within historical times seven had been recognised and utilised as medicinal herbs by modern humans. Yarrow, mallows, Ephedra and Centaury amongst them, which would still be recognised and used as herbal medicines by many people today.

The findings of the ‘flower burial’ excavation at Shanidar cave transformed our understanding of neanderthals and their likely culture and its relationship to us.

via Arkeotecnia blog

More recent work, using modern methods, has turned up some other interesting evidence from Neanderthal remains in Spain dated to around 50,000 years ago. In this case they were looking at the dental plaques and who knew so much could be discovered from such a bane of modern and apparently even ancient human life.

Applying electron and optical microscopy and GCMS analysis to the dental calculi of five individuals they came up with further evidence for both plant foods and cooking, as well some distinctive markers from common herbs. Once again yarrow turns up, this time with chamomile as well, on the basis of their characteristic constituents 4-methyl-herniarin and chamazulene respectively. Evidence for exposure to wood smoke and cooked starches was found, also some exposure to pitch or bitumen possibly used for hafting tools and implements.
The paper claims these to be the oldest food samples confirmed by a range of biochemical tests.

What will our dental plaque tell the world of 50,000 years from now?

Achillea millefolium

Interesting that yarrow, Achillea millefolium, should turn up on the west of Europe and the east in northern Iraq from 50-60,000 years ago as part of Neanderthal culture. An ancient herb already for herbalists, whose name derives from its place in the mythical stories of the classic mediterranean cultures and its place as a wound healing herb. With its broad distribution right across Eurasia and northern America, its complex taxonomy with dozens of synonyms and varieties. The vast number of common local names point to interest or selection not just a long way back for us as modern humans but perhaps to the culture of Neanderthal as well. It is often one of the introduced northern hemisphere herbs in gardens that can persist on its own just fine over here.

There is some debate over how or why Neanderthal would be eating yarrow and other herbs like chamomile. With the recently sequenced Neanderthal genome and genetic work showing they had taste receptors for bitterness like us, it seems unlikely they would’ve been consuming and utilising otherwise bitter herbs just as food.

Perhaps unsurprisingly yarrow was also noted as one of the herbs collected by European Blue Tits to line their nests which I’ve blogged on before. So even the birds seem to know about this one.

Further reading

Solecki, R. S., ‘The Implications of the Shanidar Cave Neanderthal Flower Burial’, Annals of the New York Academy of Sciences Volume 29 (July 1977), p. 114-125. Available online at:
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1977.tb41808.x/pdf
found via – http://arkeotecnia.blogspot.com.au/2011/05/bural-practices-in-neanderthals.html

Hardy et al., Neanderthal medics? Evidence for food, cooking and medicinal plants entrapped in dental calculus, Naturwissenschaften – The Science of Nature
http://dx.doi.org/10.1007/s00114-012-0942-0

Nature News – Neanderthals ate their greens http://www.nature.com/news/neanderthals-ate-their-greens-1.11030

Bitter taste perception in Neanderthals through the analysis of the TAS2R38 gene, Biology Letters, 2009, vol. 5 (6): 809-811 http://rsbl.royalsocietypublishing.org/content/5/6/809

Plant Communications

HT to Anthropogen for pointing to an interesting piece of research on plant communication.

Then via New Scientist

To the Open Access original research paper in PlosOne about an ‘other’ communication ability of plants. Or at least a Chilli seed and seedlings ability to know exactly when a Fennel is near about. Even if we try and hide it.

Fairly straightforward but fascinating science well explained that highlights what we don’t know about plant communication and senses.

Out of Sight but Not out of Mind: Alternative Means of Communication in Plants

CC license – http://www.flickr.com/photos/shishberg/

 

Which certainly made interesting reading accompanied with Do Plants Think?  at Scientific American, via the wonderful Weekly Botanical.
A review which led me to another book to put on my wish list.
http://www.whataplantknows.com/

Also of interest has the been the recent showing on local (Australian) public broadcast TV of the new BBC Scotland series How to Grow a Planet.

Based on The Emerald Planet: How Plants Changed Earths History, by Prof David Beerling. With Prof Iain Stewart, the Scottish geologist who did the previous documentary series How the Earth Made Us. He suggests himself, he has twigged onto the fact that actually plants and their production of oxygen, among other qualities, bought major and long-term changes to the atmosphere and oceans of the planet, to the state we know today and facilitated the spreading of life across the surface of the land.

A fascinating and well produced 3 part series on the significant role that microbiota, photosynthesis and eventually higher plants have played over hundreds of millions of years regarding the development of life on earth and the biodiversity we came to be within.
It is available free online (ABC iView) within Australia for a while, I guess the DVD is available elsewhere and looking around it is likely available online in other countries.

 

Synergy – Sum is greater than the parts

It’s a big topic I’m sure I’ll cover again in the future, synergy, the name we give to the phenomena that mixtures of things working together seem to have greater power than a simple sum of their component parts.

The idea is old one, from at least Aristotle’s day. Though it is a broad concept encompassing the biological and the social.

Magic bullets

Who knows where the idea that the single magic bullet is better for dealing with complex biological phenomena like disease came along. Though obviously it has been an advantageous meme to the construction and marketing of the contemporary pharmaceutical industry over the last century.

Perhaps it was the advent of modern chemistry that allowed us to separate and isolate individual constituents in long used plant drugs, to distill out their essence. Perhaps it was the germ theory, where we could imagine every disease state was simply down to the presence of a discrete and identifiable (bad) life form in isolation from any other factors. Perhaps it was the discovery of antibiotics and the initial success against the hordes of malevolent bacteria and microbes we imagined invading and destroying our bodies. Perhaps the idea of the pluripotent medicine, the cure for all ills, is something we humans have harboured for millenia. Something we imagine that can guarantee our safety and survival in what can often seem a hostile world.

In some cases for some things, there may well be a single substance that works. Though if you look at most living systems there are numerous strategies at work to survive and thrive, including beneficial relationships with other lifeforms or an array of chemical defenses in the case of plants.

I think it’s fair to say that we now realise that in fact we need the vast array of microbial lifeforms to survive, from those inside our bodies where they seem to have always outnumbered our own cells, to the broader biosphere services they perform. Though of course we don’t need them all and some of them are certainly unwelcome house guests, literally sapping the life out of us.

We can also realise by now that in fact these various lifeforms that can infect our bodies are not static, but like all lifeforms, no matter how small, they are dynamic and respond and adapt to the circumstances they face. Indeed, some of them are giving a new generation a go every 20 minutes or so. Our widespread and untempered use of antibiotics, initially seen as remarkably successful, is now fostering a swathe of multi-drug resistant (MDR) lifeforms.

In terms of pharmacology, there’s a differentiation between aspects we call pharmacokinetics, the ways and means we uptake, metabolise and excrete drug molecules, or pharmacodynamics, the ways and means drug molecules act on our own cells or those pesky germs. Of course, as typical in complex biological systems, the difference between these aspects is not necessarily always clear, but they serve a purpose for describing different ways in which the sum of a mixture is in one way or another altered, particularly made more effective. Plotted below is a representation of synergistic and antagonistic effects, indicated by the decreasing or increasing dose required of the respective drugs (A and B) for the same effect.

Herbal medicines and Malaria.

The idea of synergy in herbal medicines is a hotly contested concept by some. A contest which I believe can only be sustained with ignorance of the complex and common biology of plants and all life on earth.

Following on from the great blog about the history of Sweet Annie (Artemisia annua) and unearthed tombs in China. The use of this herb or its constituents in malaria globally and recent scientific investigations have thrown up further insights into the apparently synergistic role of whole herb medicines versus isolated constituents. This recent review (Open Access) of whole plant extracts in Malaria covers almost all the issues.

According to this recent review Artemisia annua whole herb extracts, as a fresh crushed juice or ethanolic extracts are reported to have a 6-18 fold greater activity against malaria than their artemisinin content would suggest. With casticin, a flavonoid also found in Artemisia annua, reported to increase the action of artemisinin by 3-5 fold alone.

A tea prepared traditionally as per the Chinese Pharmacopoiea gave maximum serum concentrations within 30 minutes, compared to hours for artemisinin alone, with about one fifth as much artemisinin as standard treatment alone (94.5 mg artemisinin in a tea, or 500 mg in a pill). This apparent increased bioavailability being due to the other constituents. Artemisinin being a sesquiterpene is a quite lipophilic substance and not very water-soluble, but you can dissolve more in a whole herb tea than you can alone in water, due to the amphiphilic qualities of other plant constituents, with many natural glycosides having this quality.

via http://www.stopmalarianow.org/

Curcumin, the bright yellow pigment from Tumeric, inhibits the metabolism and excretion of artemisinin too and been shown to completely inhibit the recrudesence (return) of malaria in animal models, which is a problem with artemisinin alone. Piperine from Black Pepper increases the bioavailability of curcumin itself by %2000. It also increases the bioavailability of epigallocatechin gallate (EGCG) from Green tea. The latter a known inhibitor of the efflux pumps that characterise many multi-drug resistant (MDR) organisms.

There’s plenty of evidence that synergistic effects, that alter bioavailability and potency of action, are present in whole herb extracts from single herbs (Ginkgo, St John’s Wort, Kava, Valerian, Cannabis) compared to any of the isolated constituents. Or due to different constituents in herb mixtures.

In many ways it has been the lack of sophistication and the reductionist modelling of our science that is the greatest obstacle to further understanding of all these complexities. Only now with the advent of metabolomics and genomic transcription analysis can we begin to look at the cascades and networks of effects that underly all biological systems and phenomena. In many ways this is far greater challenge to scientifically investigate and understand.

Plants themselves develop an array of physical and chemical defenses to survive. Even microbial lifeforms have a range of strategies to deal with potent drugs such as antibiotics.

In a biological sense it seems far more appropriate that we should find and expect an array of compounds, physical or pharmacological strategies, would be more successful than any one thing on its own.

further reading

Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions – Review, P Rasoanaivo, C W Wright, M L Willcox, B Gilbert, http://www.malariajournal.com/content/10/S1/S4 (Open Access)

Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood), K. Rath, K. Taxis, G. Walz, C. H. Gleiter, S.-M. Li and L. Heide, http://www.ajtmh.org/content/70/2/128.short

The importance of pharmacological synergy in psychoactive herbal medicines, M. Spinella, http://www.ncbi.nlm.nih.gov/pubmed/11991792

Review (Part I) – Synergy research: Approaching a new generation of phytopharmaceuticals, H. Wagner, G. Ulrich-Merzenich, http://dx.doi.org/10.1016/j.phymed.2008.12.018

Review (Part II) – New perspectives for synergy research with the “omic”-technologies, G. Ulrich-Merzenich, D. Panek, H. Zeitler, H. Wagner, H. Vetter, http://dx.doi.org/10.1016/j.phymed.2009.04.001

Blue Tits and the ‘Potpourri’ hypothesis

European Blue Tit – CC photo credit – marko_k

Following the bees, now the birds and more on the neologism pharmacophory*.

Other members of the animal world have been documented to ingest plant or mineral substances apparently in response to infection and illness. Though so far only a few have been documented to apply herbal or other natural substances in their local environment or around their dwellings.

One other animal that has been documented to also collect plant material containing pharmacologically active constituents is the European Blue Tit. A series of recent papers describe how it was found that Blue Tits collected foliage from highly aromatic herbs, Yarrow, Lavenders, Mints, Thyme, Pine even Eucalyptus (introduced to Mediterranean Europe), to line their nests. The presence in the nest of specific aromatic plants having a greater representation than would be expected compared to the immediately available surrounding flora, indicating an active seeking and collecting of this material for nests. The birds even replacing it when those pesky researchers had removed it to see what the birds did.

Blue Tit nest with a clutch of eggs – CC photo credit – fsphil

It probably isn’t just for decoration either, as they discovered that the aromatic foliage benefited the chicks through increased weight gain and feather development and higher hematocrit levels in their blood. The aromatic plant material contains anti-bacterial, anti-fungal and other active constituents that reduce the parasite and microbial burden and appears to be derived from a range of aroma types. Hence the Potpourri hypothesis, where a broad range of aroma types represent a broader spectrum of constituents or may mask the scent of chicks to predators or deter blood suckers like mosquitos. Perhaps they even help with attracting mates.

Picture credit – wonderful shot from Words @ Everything is Permuted

*Pharmacophory – literally ‘carrying’ or ‘moving of drugs’, was the neologism applied to the increased collection of propolis and application around the hive by bees when their hive was infected with the chalkbrood fungus mentioned in a previous post. Somewhere between the human use of antiseptics, incenses or mozzie and insect repellents, aromatherapy and preventative medicine it seems to me. Science is a boon for deriving precise but obscure classic terms for often seemingly mundane phenomena or experience. Seems like good one to me.

Refs.

Aromatic herbs in Corsican blue tit nests: The ‘Potpourri’ hypothesis
Aromatic plants in nests of blue tits: positive effects on nestlings
Aromatic Plants in Eurasian Blue Tit Nests: The ‘Nest Protection Hypothesis’ Revisited

Snake Root and Medical misinterpretations

Could a 50-year-old pillar of modern psychiatry be based on a misunderstanding of an ancient herbal medicine and the already available evidence? Some researchers have suggested just that.

Notwithstanding the real and significant personal and social toll that mental health problems play in many people’s lives in the modern world. Our true understanding of what is happening physiologically still seems far from certain.

Perhaps no-one is sure quite where it was first applied as a medicine, likely a long time ago. Though Sarpagandha, aka Snake root, or Rauwolfia serpentina, looks like a relatively insignificant small woody shrub most of the time, but it is showy and distinctive when in flower and is found growing in forested regions from the Indian subcontinent to south-east Asia.

Rauwolfia serpentina from Hortus Malabaricus 1678-1703

The many historical synonyms and local names attest to the use of this plant in folk and traditional medicine for a considerable time across much of its range in Asia. Though it seems there was added botanical confusion for a while from multiple naming and typos. Rauvolfia or Rauwolfia?

As for many traditional medicines its indications are broad, but often focus on treatment for poisons, gastrointestinal infections including worms and yes even snake bite. One ancient Sanskrit name however, Chandra – the moon, refers to its use in ‘moon’s disease’, aka ‘lunacy’. So that seems to make that an ancient reference to mental illness to me.

It was (re-) introduced to the western world roughly 70 years ago, from the Ayurvedic medicine tradition of India, after the publication by Indian doctors on the effectiveness of the herb in both hypertension and mania in the 1930’s and 40’s. Reportedly a widely utilised and popular herb by the turn of the 20^th century in India, Ghandhi is often cited as apparently utilising the relaxing qualities of this herb as a tea on a regular basis. Whilst that may or may not be the case, it certainly seems to have been a significant element of the local herb trade for centuries or millenia by then.

The pharmacological activity of this herb radically altered theories and perceptions of cardiovascular and neurological pharmacology then in the west. Though perhaps mistakenly some of those early ideas have also remained with us and to a large extent have been unquestioned since then.

Early clinical studies in the US reported dramatic results in hypertension, particularly in young “psychoneurotic” patients with tachycardia according to one early review of the herb. Whilst most of the Indian and earlier clinical studies used the whole herb extract, the isolation and identification of reserpine in the root soon led to investigations and clinical trials of this single constituent alone. As has been the case for most of the still used pharmaceuticals derived directly from herbal medicines in the world of pharma science, which includes reserpine.

Even in the mid 1950’s there was recognition that there was a varying mix of alkaloids in Rauwolfia, that could depend on source region and age, plus some early debate on the merits of whole herb versus reserpine alone. Not unexpectedly perhaps, some pharmaceutical companies were marketing the pure alkaloid for treatment by 1954, most widely under the name Serpasil. It soon became evident that long-term treatment with high doses of reserpine induced some serious negative symptoms in people. Causing reduced activity and apparent central nervous system depression.

1956 Serpasil ad from CIBA

Following reports of its use in India for mental disorders, schizophrenics were also treated with reserpine, which didn’t cure them but was sedating and anxiety reducing. It became popularly prescribed for mental disorders for a while.

Along with other findings such as monoamine oxidase inhibitors showing antidepressant action, came the discovery that reserpine acts by permanently inhibiting the transport proteins of our monoamine neurotransmitters (serotonin, dopamine, norepinephrine) into vesicles within neurons. This depletion over time of neurotransmitters caused a general shutdown of what are excitatory pathways of the central nervous system, ie. causes diminished activity. This of course is part of the reason why it is effective in overly excited states like mania.

Stopping reserpine allows the body to regenerate the proteins necessary for neurotransmitter transport over days and weeks, and gradually return to baseline function. This discovery, with other findings, came to be used in part as evidence for the so-called monoamine or serotonin hypothesis. A thesis that an ‘imbalance’ of one or more of these brain messengers is the cause of a whole host of mental disorders, particularly and popularly serotonin for depression in recent times. Though some researchers who have looked back through the data and reports of over 50 years ago are now asking the question about how valid or useful the serotonin hypothesis has been.

There appears to have been few if any reported cases of severe symptoms in the traditional use of the whole herb containing a mixture of alkaloids. It seems unlikely to have been taken endlessly or without reasons, as like many traditional herbal medicine preparations (often a tea) the intense bitterness is a generally a self-limiting factor on consumption for anyone but the ill.

The discovery of these pharmacological actions and the serotonin or monoamine hypothesis spawned whole new classes of psychiatric drugs, anti-psychotics and Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants in particular. Also reserpine remains in use for some types of hypertension to this day. Setting aside the brawl over the actual diagnosis of depression, so widely given in contemporary times. The hypothesis also saw a boom in the development of pharmaceutical agents targeting serotonin metabolism and action. However the lack of evidence of  effectiveness better than placebo for leading SSRI and other antidepressants, despite the marketing and billions spent on research or even the attempts to hide data away, seems to question the whole hypothesis more than support it.

Serotonin of course plays a role in many other aspects of physiology as well, being originally identified both as an agent from blood serum that caused vasoconstriction (sero-tonin) and as a gastrointestinal smooth muscle stimulant (originally named enteramine). Serotonin is also found in many plants, particularly seeds, some of them are common foods – particularly black walnuts, also pecans, banana, kiwifruit, pineapple, avocado and more.

Physiology of all living things seems to be a complex network of different systems, hopefully working in a kind of organised fashion together depending upon the internal and external environment. Although reductionist science appears to be focused on a mechanistic model, the magic bullet or single factor responsible. Life itself seems a lot more complicated than that in practice.

Rauwolfia serpentina from Curtis Botanical Magazine 1804

Rauwolfia serpentina has been listed in the CITES Annex for trade in medicinal plants. Though it seems to remain unknown how endangered it is, it’s continuing use in traditional medicines or as a source of reserpine and dramatic changes across its habitat in a world full of people are risk factors for unsustainability and loss of wild populations. Tissue and cell culture have been tried, synthesis of reserpine is complex and expensive. Cultivation projects in some countries (India, Pakistan) have been undertaken. Other plants also contain reserpine but it seems are not currently used as a source. Other related alkaloids from Rauwolfia and some closely related genera continue to see use in medicine or in research of treatments for mental health and other disorders.

Reading matters – The Beginning and End of Western Botanical Sciences?

Been reading more than writing lately, and thought I’d share a few interesting posts and stories concerning the beginning and possible ending of field and practical botanical science in the western world.

Starting with the excellent ArtPlantae blog and their posts about the intriguing German/Dutch naturalist Georgius Everhardus Rumphius over April and the republished English translation of his seminal volumes on Indonesian and SE Asian foods, medicines and spices, The Ambonese Herbal.

A quite remarkable tale from the 17^th and 18^th centuries, it is a wonder the beautiful botanical art and original descriptions ever made it to print and are again available over 300 years later.

The history of the Dutch East Indies Company, or for that matter the British East India Company, and the spice trade of the 17^th century is littered with incredible calamity and conflict, for locals often. Making it perhaps all the more remarkable that Rumphius was able to create such a work of ethnobotanical and natural science significance amidst all that.

Georgius Everhardus Rumphius, Soldier & Naturalist

Rumphius: A Naturalist for the People

Inside ‘The Ambonese Herbal’

I have seen it yet though wish I could.

The Ambonese Herbal – 6 volume reprint with English translation

The original Latin/Dutch version of The Ambonese Herbal can be found at Botanicus.org

There are numerous other historical herbal and botanical texts back to the 16th century also available online or as pdf downloads at the great Botanicus.org site using material from the Missouri Botanic Gardens Library.

So 300+ years after Rumphius, through the industrial revolution, deep into the end game of the age of fossil fuel and oil, how does the future of practical botanical science in western society and the documentation of the world’s botanical diversity look?

Well students in agriculture and botanical sciences appear to be mostly absent or perhaps the opportunities, recognition or funding are not there. The ever more urbanised human world means many are simply alienated from understanding the importance of plants and biodiversity in a functioning global ecosphere and local ecosystems.

Aside from a few large botanical gardens, in a seemingly ever more corporatised world, where are resources and recognition for this work of cataloguing and understanding of the world’s biodiversity going to come from?

Another ArtPlantae post and this recent Nature article (via Among The Stately Trees) ponder some of the many issues.

Though interest in plants, gardening, herbs and ethnobotany amongst the public seems high, overall it seems inevitable that the general level of direct and practical knowledge of plants in human civilisation is on the way down.

Despite that I think plants will be vital for human existence on earth forever. Increasing ignorance I’m certain does us no good in the long run.

I’m sure there will aways be interest, it’s kind of necessary for someone to know enough for us all to survive. Though perhaps it will reside more in the gardeners and amateur naturalists rather than institutions like universities and their generally more corporatised interests these days.

The last botany student in the UK

Plant collectors becoming as rare as the plants they seek

Superstars of botany: Rare specimens

A handful of plant collectors has shaped the field of botany. Now they are disappearing, and there are no clear successors.