Tag: traditional medicine

Categories : General InterestTags :

500-year-old Horn Container Discovered in South Africa Sheds Light on Pre-colonial Khoisan Medicines

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Both the Khoi and the San believed in a mythical animal, resembling a cow, whose horns were thought to have medicinal attributes. Credit: Rodger Smith

By Justin Bradfield, The Conversation

In 2020, a chance discovery near the small South African hamlet of Misgund in the Eastern Cape unearthed an unusual parcel – a gift to science. The parcel turned out to be a 500-year-old cow horn, capped with a leather lid and carefully wrapped in grass and the leafy scales of a Bushman poison bulb (Boophane disticha). Inside the horn were the solidified remnants of a once-liquid substance.

Thanks to chemical analyses, we now know that the horn was a medicine container. It is the earliest known object of its kind from anywhere in southern Africa and offers the first insights into pre-colonial medicines in this part of the world.

My colleagues and I conducted chemical analyses of the contents. We identified several secondary plant metabolites, the most abundant of which were mono-methyl inositol and lupeol. Both of these compounds, and indeed all of those identified, have known medicinal properties.

This remarkable find is the oldest example in southern Africa, of which we are aware, of two or more plant ingredients being purposefully combined into a container to form a medicinal recipe. Several museums in South Africa house examples of medicine horns collected during the 19th and 20th centuries – but none has ever been found in an archaeological context.

Various plant uses

The medicine container was found in a painted rock shelter. A radio carbon date of the horn container places the parcel at around AD 1461-1630. Although the rock shelter contains several San paintings, we do not know if they are the same age as the horn container. At this time the area was occupied by both San hunter-gatherers and Khoi pastoralists; both believed in a mythical animal, resembling a domestic cow, whose horns were considered to have medicinal attributes.

People have exploited the pharmacological properties of plants for at least the last 200 000 years. The descendants of these communities still live in Southern Africa today. During the Middle Stone Age (which started about 300 000 years ago and ended between 50 000 and 20 000 years ago), people burnt certain aromatic leaves to fumigate their sleeping areas. Plant extracts also seem to have been the main component of glues and adhesives and hunting poisons around this time.

But not much is known about traditional medicines from the pre-colonial era of southern Africa. What information there is derives mainly from early traveller accounts and modern ethnographic studies. The horn offered us a chance to learn a little more about traditional knowledge of medicine and pharmacology during this early period.

The descendants of these communities still live in southern Africa today.

Medical and spiritual applications

The main compounds present in the container, mono-methyl inositol and lupeol, are still found today in a variety of known medicinal plants in the Eastern Cape. They have a wide range of recorded medicinal applications, including the control of blood sugar and cholesterol levels, and treatment of fevers, inflammation and urinary tract infections. They can also be applied topically to treat infections – rubbing ointment into cuts in the skin is one of the ways the San are known to have administered certain medicines.

Both mono-methyl inositol and lupeol are pharmacologically safe compounds. This means that they can be ingested without the risk of overdose. Both compounds stimulate the production of dopamine in the brain; mono-methyl inositol is used to treat anxiety, and plants containing lupeol are used as aphrodisiacs.

For the Khoi and San people, not all medicines were meant to treat physiological illnesses. Healers were specialised individuals whose task was to treat both physical and spiritual ailments. Indeed, one of the principal functions of traditional medicine, both in the past and today, is to treat supernatural bewitchment. Medicine and culture remain intimately entwined and traditional medicine, which is highly adaptive, continues to play an important role in much of Africa as a primary health service.

A treasured possession

We cannot know exactly what the medicine stored in the horn was used for, how it was administered or who precisely used it. But it was clearly a treasured possession, judging by the way it was carefully wrapped and deposited in the rock shelter. Its owner evidently intended to retrieve it but never returned.

The absence of any evidence of long-term occupation of the shelter means that the medicine horn is an isolated, chance discovery. Nevertheless, this is a find that sheds new light on traditional medicines used in the Eastern Cape 500 years ago.

This article is republished from The Conversation under a Creative Commons license.

Source: The Conversation

Categories : Mental Health New Compounds and TreatmentsTags :

Scientists Create Antidepressant Drug Candidates from Traditional African Plant Medicine

On By ModernMedia
Photo by Octavian Dan on Unsplash

Scientists have developed two new drug candidates for potentially treating addiction and depression, modelled on the pharmacology of a traditional African psychedelic plant medicine called ibogaine. At very low doses, these new compounds were able to blunt symptoms of both conditions in mice.

The study, published in Cell, took inspiration from ibogaine’s impact on the serotonin transporter (SERT), which is also the target of selective serotonin reuptake inhibitor (SSRI) drugs, such as fluoxetine. A team of scientists from UC San Francisco and Yale and Duke universities virtually screened 200 million molecular structures to find ones that blocked SERT in the same way as ibogaine.

“Some people swear by ibogaine for treating addiction, but it isn’t a very good drug. It has bad side effects, and it’s not approved for use in the US,” said Brian Shoichet, PhD, co-senior author and professor in the UCSF School of Pharmacy. “Our compounds mimic just one of ibogaine’s many pharmacological effects, and still replicate its most desirable effects on behaviour, at least in mice.”

Dozens of scientists from the laboratories of Shoichet, Allan Basbaum, PhD, and Aashish Manglik, MD, PhD, (UCSF); Gary Rudnick, PhD, (Yale); and Bill Wetsel, PhD, (Duke) helped demonstrate the real-world promise of these novel molecules, which were initially identified using Shoichet’s computational docking methods.

Docking involves systematically testing virtual chemical structures for binding with a protein, enabling scientists to identify new drug leads without having to synthesise them in the lab. “This kind of project begins with visualizing what kinds of molecules will fit into a protein, docking the library, optimising and then relying on a team to show the molecules work,” said Isha Singh, PhD, a co-first author of the paper who did the work as a postdoc in Shoichet’s lab. “Now we know there’s a lot of untapped therapeutic potential in targeting SERT.”

Optimising a shaman’s cure

Ibogaine is found in the roots of the iboga plant, which is native to central Africa, and has been used for millennia during shamanistic rituals. In the 19th and 20th centuries, doctors in Europe and the US experimented with its use in treating a variety of ailments, but the drug never gained widespread acceptance and was ultimately made illegal in many countries.

Part of the problem, Shoichet explained, is that ibogaine interferes with many aspects of human biology.

“Ibogaine binds to hERG, which can cause heart arrhythmias, and from a scientific standpoint, it’s a ‘dirty’ drug, binding to lots of targets beyond SERT,” Shoichet said. “Before this experiment, we didn’t even know if the benefits of ibogaine came from its binding to SERT.”

Shoichet, who has used docking on brain receptors to identify drugs to treat depression and pain, became interested in SERT and ibogaine after Rudnick, an expert on SERT at Yale, spent a sabbatical in his lab. Singh picked up the project in 2018, hoping to turn the buzz around ibogaine into a better understanding of SERT.

It was the Shoichet lab’s first docking experiment on a transporter – a protein that moves molecules into and out of cells – rather than a receptor. One round of docking whittled the virtual library from 200 million to just 49 molecules, 36 of which could be synthesised. Rudnick’s lab tested them and found that 13 inhibited SERT.

The team then held virtual-reality-guided “docking parties,” to help Singh prioritise five molecules for optimization. The two most potent SERT inhibitors were shared with Basbaum and Wetsel’s teams for rigorous testing on animal models of addiction, depression and anxiety.

“All of a sudden, they popped – that’s when these drugs looked a lot more potent than even paroxetine [Paxil],” Shoichet said.

Manglik, an expert with cryo-electron microscopy (cryo-EM), confirmed that one of the two drugs, dubbed ‘8090,’ fit into SERT at the atomic level in a way that closely resembled Singh and Shoichet’s computational predictions. The drugs inhibited SERT in a similar way to ibogaine, but unlike the psychedelic, their effect was potent and selective, with no spillover impacts on a panel of hundreds of other receptors and transporters.

“With this sort of potency, we hope to have a better therapeutic window without side effects,” Basbaum said. “Dropping the dose almost 200-fold could make a big difference for patients.”

Source: University of California – San Francisco

Categories : New Compounds and TreatmentsTags :

Native American Plant Remedies Found to Have Dual Properties

On By ModernMedia
Photo by Sebastian Unrau on Unsplash

Following a functional screen of extracts from US plants researchers found that plants with a long history of use by Native Americans as topical analgesics were often also used as gastrointestinal aids.

The study, published today in Frontiers in Physiology, found forest plants that activated the KCNQ2/3 potassium channel, a protein that passes electrical impulses in the brain and other tissues, showed a long history of use by Native Americans as topical analgesics, to treat conditions such as insect bites, stings, sores and burns. Less intuitively, the same plants that activated KCNQ2/3 and were used as traditional painkillers were often also used as gastrointestinal aids, especially for preventing diarrhoea.

“Done in collaboration with the US National Parks Service, this study illustrates how much there is still to learn from the medicinal practices of Native Americans, and how, by applying molecular mechanistic approaches we can highlight their ingenuity, provide molecular rationalizations for their specific uses of plants, and potentially uncover new medicines from plants,” said UCI School of Medicine professor Geoffrey Abbott, PhD.
KCNQ2/3 is present in nerve cells that sense pain, and activating it would relieve pain by reducing pain signal transmission. The breakthrough \came when the team discovered that the same plant extracts that activate KCNQ2/3 have an opposite effect on the related intestinal potassium channel, KCNQ1-KCNE3. Previous studies on modern medicines showed that KCNQ1-KCNE3 inhibitors can prevent diarrhoea.

The Abbott Lab is currently screening native US plants, having shown already that quercetin and tannic and gallic acids explained many of the beneficial effects of the plants. The team also identified binding sites on the channel proteins that produce the effects.

Knowing that these compounds activate versus inhibit closely related human ion channel proteins, drug specificity and safety can be improved and therefore safety. More specifically, the plant compounds can be further optimised with the goal of treating pain and secretory diarrhoea.

“I personally am very excited about the paper; it was my lab’s first published collaboration with the National Park Service, and it shines a light on the incredible ingenuity and medicinal wisdom of Californian Native American tribes,” said Prof Abbott.

New analgesics are being sought to fight the opioid crisis. In addition, according to the CDC, diarrhoeal diseases account for 1 in 9 child deaths worldwide; incredibly, diarrhoea kills over 2000 children every day worldwide – more than AIDS, malaria and measles combined.

Source: University of California – Irvine