Tag: traditional medicine

Herbal Compound Found to Kill TB in the Inactive State

Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash

A compound found in African wormwood – a plant used medicinally for thousands of years to treat many types of illness – could be effective against tuberculosis, according to a new study available online in the Journal of Ethnopharmacology.

The team, co-led by Penn State researchers, found that the chemical compound, an O-methylflavone, can kill Mycobacterium tuberculosis, or Mtb, that causes tuberculosis in both its active state and its slower, hypoxic state, which the mycobacteria enters when it is stressed.

Bacteria in this state are much harder to destroy and make infections more difficult to clear, according to co-corresponding author Joshua Kellogg, assistant professor of veterinary and biomedical sciences in the College of Agricultural Sciences.

While the findings are preliminary, Kellogg said the work is a promising first step in finding new therapies against tuberculosis.

“Now that we’ve isolated this compound, we can move forward with examining and experimenting with its structure to see if we can improve its activity and make it even more effective against tuberculosis,” he said. “We’re also still studying the plant itself to see if we can identify additional molecules that might be able to kill this mycobacterium.”

Tuberculosis is one of the world’s leading killers among infectious diseases, according to the Centers for Disease Control and Prevention. There are about 10 million cases a year globally, with approximately 1.5 million of those being fatal.

While effective therapies exist for TB, the researchers said there are several factors that make the disease difficult to treat. A standard course of antibiotics lasts six months, and if a patient contracts a drug-resistant strain of the bacteria, it stretches to two years, making treatment costly and time consuming.

Additionally, the bacteria can take two forms in the body, including one that is significantly harder to kill.

“There’s a ‘normal’ microbial bacterial form, in which it’s replicating and growing, but when it gets stressed – when drugs or the immune system is attacking it – it goes into a pseudo-hibernation state, where it shuts down a lot of its cellular processes until it perceives that the threat has passed,” Kellogg said. “This makes it really hard to kill those hibernating cells, so we were really keen to look at potential new chemicals or molecules that are capable of attacking this hibernation state.”

Multiple species of the Artemisia plant have been used in traditional medicine for centuries, the researchers said, including African wormwood, which has been used to treat cough and fever. Recent studies in Africa have suggested that the plant also has clinical benefits in treating TB.

“When we look at the raw plant extract that has hundreds of molecules in it, it’s pretty good at killing TB,” Kellogg said. “Our question was: There seems to be something in the plant that’s really effective – what is it?”

For their study, the researchers took raw extract of the African wormwood plant and separated it into “fractions” – versions of the extract that have been separated into simpler chemical profiles. They then tested each of the fractions against Mtb, noting whether they were effective or ineffective against the bacteria. At the same time, they created a chemical profile of all of the tested fractions.

“We also used machine learning to model how the changes in chemistry correlated with the changes in activity that we saw,” Kellogg said. “This allowed us to narrow our focus to two fractions that were really active.”

From these, the researchers identified and tested a compound that effectively killed the bacteria in the pathogen’s active and inactive states, which the researchers said is significant and rare to see in TB treatments. Further testing in a human cell model showed that it had minimal toxicity.

Kellogg said the findings have the potential to open new avenues for developing new, improved therapeutics.

“While the potency of this compound is too low to use directly as an anti-Mtb treatment, it may still be able to serve as the foundation for designing more potent drugs,” he said. “Furthermore, there appear to be other, similar chemicals in African wormwood that may also have the same type of properties.”

The researchers said that in the future, more studies are needed to continue exploring the potential for using African wormwood for treating TB.

Source: Penn State

Self-medicating Gorillas and Traditional Healers Provide Clues for New Drug Discovery

Four plants eaten by gorillas, also used in Gabonese traditional medicine, have antibacterial effects

Four plants consumed by wild gorillas in Gabon and used by local communities in traditional medicine show antibacterial and antioxidant properties, find Leresche Even Doneilly Oyaba Yinda from the Interdisciplinary Medical Research Center of Franceville in Gabon and colleagues in a new study publishing September 11 in the open-access journal PLOS ONE.

Wild great apes often consume medicinal plants that can treat their ailments. The same plants are often used by local people in traditional medicine.

To investigate, researchers observed the behavior of western lowland gorillas (Gorilla gorilla gorilla) in Moukalaba-Doudou National Park in Gabon and recorded the plants they ate. Next, they interviewed 27 people living in the nearby village of Doussala, including traditional healers and herbalists, about the plants that were used in local traditional medicine. The team identified four native plant species that are both consumed by gorillas and used in traditional medicine: the fromager tree (Ceiba pentandra), giant yellow mulberry (Myrianthus arboreus), African teak (Milicia excelsa) and fig trees (Ficus). They tested bark samples of each plant for antibacterial and antioxidant properties and investigated their chemical composition.

The researchers found that the bark of all four plants had antibacterial activity against at least one multidrug-resistant strain of the bacterium Escherichia coli. The fromager tree showed “remarkable activity” against all tested E. coli strains. All four plants contained compounds that have medicinal effects, including phenols, alkaloids, flavonoids, and proanthocyanidins. However, it’s not clear if gorillas consume these plants for medicinal or other reasons.

Biodiverse regions, such as central Africa, are home to a huge reservoir of unexplored and potentially medicinal plants. This research provides preliminary insights about plants with antibacterial and antimicrobial properties, and the four plants investigated in this study might be promising targets for further drug discovery research – particularly with the aim of treating multidrug-resistant bacterial infections.

The authors add: “Alternative medicines and therapies offer definite hope for the resolution of many present and future public health problems. Zoopharmacognosy is one of these new approaches, aimed at discovering new drugs.”

Provided by PLOS

Ancient Medicinal Minerals Inspire New Tissue Repair Technology

Photo by MJ RAHNAMA

For centuries, civilizations have used naturally occurring, inorganic materials for their perceived healing properties. Egyptians thought green copper ore helped eye inflammation, the Chinese used cinnabar for heartburn, and Native Americans used clay to reduce soreness and inflammation.

Today, researchers at Texas A&M University are still discovering ways that inorganic materials can be used for healing.

In two recently published articles, Dr Akhilesh Gaharwar, a Tim and Amy Leach Endowed Professor in the Department of Biomedical Engineering, and Dr Irtisha Singh, assistant professor in the Department of Cell Biology and Genetics, uncovered new ways that inorganic materials can aid tissue repair and regeneration.

The first article, published in Acta Biomaterialia, explains that cellular pathways for bone and cartilage formation can be activated in stem cells using inorganic ions. The second article, published in Advanced Science, explores the usage of mineral-based nanomaterials, specifically 2D nanosilicates, to aid musculoskeletal regeneration.

“These investigations apply cutting-edge, high-throughput molecular methods to clarify how inorganic biomaterials affect stem cell behavior and tissue regenerative processes,” Singh said.

The ability to induce natural bone formation holds promise for improvements in treatment outcomes, patient recovery times and the reduced need for invasive procedures and long-term medication.

“Enhancing bone density and formation in patients with osteoporosis, for example, can help mitigate the risks of fractures, lead to stronger bones, improve quality of life and reduce healthcare costs,” Gaharwar said. “These insights open up exciting prospects for developing next-generation biomaterials that could provide a more natural and sustainable approach to healing.”

Gaharwar said the newfound approach differs from current regeneration methods that rely on organic or biologically derived molecules and provides tailored solutions for complex medical issues.

“One of the most significant findings from our research is the ability of these nanosilicates to stabilise stem cells in a state conducive to skeletal tissue regeneration,” he said. “This is crucial for promoting bone growth in a controlled and sustained manner, which is a major challenge in current regenerative therapies.”

Gaharwar recently received a grant for his work in using inorganic biomaterials in conjunction with 3D bioprinting techniques to design custom bone implants for reconstructive injuries.

“In reconstructive surgery, particularly for craniofacial defects, induced bone growth is crucial for restoring both function and appearance, vital for essential functions like chewing, breathing and speaking,” he said. “Inducing bone formation has several critical applications in orthopaedics and dentistry.”

“This approach not only bridges ancient practices with modern scientific methods but also minimises the use of protein therapeutics, which carry risks of inducing abnormal tissue growth and cancerous formations,” Gaharwar said. “Collectively, these findings elucidate the potential of inorganic biomaterials to act as powerful mediators in tissue engineering and regenerative strategies, marking a significant step forward in the field.”

Source: Texas A&M University

Medicinal Plants Help Keep Children Healthy in South Africa: 61 Species were Recorded

The common yellow commelina, one of the popular plants used to treat children. Photo by Bernard DUPONT via Wikimedia Commons. CC2.0

In 2021, almost 33 of every 1 000 South African children under five years old died.

This under-five mortality rate is far worse than in similar middle-income countries such as Brazil (14.4 per 1000 births), Cuba (5 per 1000), India (30.6), Indonesia (22.2) and Egypt (19.0).

South Africa’s under-five mortality rate also lags behind the UN’s Sustainable Development Goal of reducing these figures worldwide by 2030 to 25 deaths per 1000.

Significant progress has been made. In 1994, South Africa’s under-five mortality rate was 60.4 per 1000. The government’s Expanded Programme on Immunisation was one health intervention that made a difference.

However, inequalities persist. The underfunded public health sector has been stretched to serve 71% of the population.

Worldwide, many people, particularly those in rural settlements, depend on medicinal plants for their health. In August 2023, the World Health Organization held the first global summit on traditional medicine, in India.

As researchers with an interest in indigenous knowledge, we explored the use of medicinal plants as remedies against diseases among children in the North West province of South Africa.

Of the province’s population, 49.2% live below the poverty line with no access to proper housing, water and sanitation. These conditions have an impact on children’s health.

Despite the high reliance on traditional medicine by rural populations, the role of medicinal plants for the treatment of childhood diseases remains speculative and lacks systematic documentation.

Our study yielded the first comprehensive inventory of medicinal plants and indigenous knowledge related to children’s healthcare in the area.

In total, 61 plants from 34 families were recorded as medicine used for managing seven categories of diseases. Skin-related and gastro-intestinal diseases were the most prevalent childhood health conditions encountered by the study participants.

Capturing local wisdom

Evidence shows traditional health practitioners continue to play an important role in managing childhood illness in sub-Saharan Africa.

South Africa is endowed with a rich wealth of flora and is often acclaimed as a biodiversity hotspot. Thousands of plants are used for traditional medicine for the management of diverse health conditions.

In the North West, we interviewed 101 participants, including traditional health practitioners, specifically those with expertise in managing and treating diseases among children, and herbal vendors operating in the selected study areas.

Gender distribution among the participants was 78% female and 21% male. This signifies the importance of women as active custodians of indigenous knowledge related to childhood health needs.

Of the participants, 63% had completed a secondary level of education, 21.8% had no formal education and 5% had attended primary school. Although 79% of the participants lived in villages, 15.8% were based in urban areas.

The participants were asked which plants they used to treat children. Of the 61 plants identified, 89% were recorded for the first time as botanicals used for childhood-related diseases by traditional health practitioners.

Carpet plant (Geranium incanum), common yellow commelina (Commelina africana) and elephant’s root (Elephantorrhiza elephantina) were the most popular medicinal plants.

Carpet plant was used as a treatment for diverse health problems such as umbilical cord conditions, muscle fits, measles, weight loss and appetite loss.

Common yellow commelina was used as a remedy to treat skin conditions, while elephant’s root was used to treat gastrointestinal and skin diseases.

Roots and rhizomes were the parts most frequently used as treatments (40%), followed by leaves (23%) and whole plants (20%).

Boiling plants or softening them in liquid were the main preparation methods. The plant remedies were mainly administered orally (60%) and used on the skin (39%).

The study also confirmed there are similarities in indigenous practices, techniques and plant matter for specific conditions that were previously reported in other provinces: KwaZulu-Natal and the Eastern Cape.

The way forward

There is increasing support from governments for promoting traditional medicine as part of primary healthcare in African countries such as Cameroon and South Africa.

We recommend that:

  1. Government provide institutional and financial support to determine the role of herbal medicine in primary healthcare. Working with traditional health practitioners, medicinal plants must be documented and testing laboratories need to be set up to establish their efficacy and to determine appropriate dosages.
  2. Botanical gardens should be created to ensure the sustainability of plants and their continued role in providing much-needed medical care. In the North West province, 40% of the ecosystems are under severe stress, with 11 of the 61 vegetation and 14 of the 18 river types classified as threatened. Medicinal plants are mostly harvested from the wild, so it’s possible that many could face extinction from uncontrolled harvesting.

Authors

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

South Africa’s Traditional Medicines Should be Used in Modern Health Care

Both the Khoi and the San believed in a mythical animal, resembling a cow, whose horns were thought to have medicinal attributes. This centuries-old medicine horn contained herbal remedies used by the Khoi-san. Credit: Rodger Smith

By Zelna Booth

Traditional medicines are part of the cultural heritage of many Africans. About 80% of the African continent’s population use these medicines for healthcare.

Other reasons include affordability, accessibility, patient dissatisfaction with conventional medicine, and the common misconception that “natural” is “safe”.

The growing recognition of traditional medicine resulted in the first World Health Organization global summit on the topic, in August 2023, with the theme “Health and Wellbeing for All”.

Traditional medicines are widely used in South Africa, with up to 60% of South Africans estimated to be reliant on traditional medicine as a primary source of healthcare.

Conventional South African healthcare facilities struggle to cope with extremely high patient numbers. The failure to meet the basic standards of healthcare, with increasing morbidity and mortality rates, poses a threat to the South African economy.

In my opinion, as a qualified pharmacist and academic with a research focus on traditional medicinal plant use in South Africa, integrating traditional medicine practices into modern healthcare systems can harness centuries of indigenous knowledge, increasing treatment options and provide better healthcare.

Recognition of traditional medicine as an alternative or joint source of healthcare to that of standard, conventional medicine has proven challenging. This is due to the absence of scientific research establishing and documenting the safety and effectiveness of traditional medicines, along with the lack of regulatory controls.

What are traditional medicines?

Traditional medicine encompasses a number of healthcare practices aimed at either preventing or treating acute or chronic complaints through the application of indigenous knowledge, beliefs and approaches. It incorporates the use of plant, animal and mineral-based products. Plant-derived products form the majority of treatment regimens.

Traditional medicine practices also have a place in ritualistic activities and communicating with ancestors.

South Africa is rich in indigenous medicinal fauna and flora, with about 2000 species of plants traded for medicinal purposes. In South Africa the provinces of KwaZulu-Natal, Gauteng, Eastern Cape, Mpumalanga and Limpopo are trading “hotspots”. The harvested plants are most often sold at traditional medicine muthi markets.

Uses of medicinal plants

Medicinal plants most popularly traded in South Africa include buchu, bitter aloe, African wormwood, honeybush, devil’s claw, hoodia, African potato, fever tea, African geranium, African ginger, cancer bush, pepperbark tree, milk bush and the very commonly consumed South African beverage, rooibos tea.

The most commonly traded medicinal plants in South Africa are listed below along with their traditional uses:

Buchu – Urinary tract infections; skin infections; sexually transmitted infections; fever; respiratory tract infections; high blood pressure; gastrointestinal complaints.

Bitter aloe – Skin infections; skin inflammation; minor burns.

African wormwood – Respiratory tract infections; diabetes, urinary tract disorders.

Honeybush – Cough; gastrointestinal issues; menopausal symptoms.

Devil’s claw – Inflammation; arthritis; pain.

Hoodia – Appetite suppressant.

African potato – Arthritis; diabetes; urinary tract disorders; tuberculosis; prostate disorders.

Fever tea – Respiratory tract infections; fever; headaches.

African geranium – Respiratory tract infections.

African ginger – Respiratory tract infections; asthma.

Cancer bush – Respiratory tract infections; menstrual pain.

Pepperbark tree – Respiratory tract infections; sexually transmitted infections.

Milk bush – Pain; ulcers; skin conditions.

Rooibos – Inflammation; high cholesterol; high blood pressure.

There are many ways in which traditional medicine may be used. It can be a drop in the eye or the ear, a poultice applied to the skin, a boiled preparation for inhalation or a tea brewed for oral administration.

Roots, bulbs and bark are used most often, and leaves less frequently. Roots are available throughout the year. There’s also a belief that the roots have the strongest concentration of “medicine”. Harvesting of the roots, however, poses concerns about the conservation of these medicinal plants. The South African government, with the draft policy on African traditional medicine Notice 906 of 2008 outlines considerations aimed at ensuring the conservation of these plants through counteracting unsustainable harvesting practises.

Obstacles to traditional medicine use

The limited research investigating interactions posed should a patient be making use of both traditional and conventional medicine is a concern.

During the COVID-19 pandemic, many patients used traditional remedies for the prevention of infection or treatment.

Understanding which traditional medicines are being used and how, their therapeutic effects in the human body, and how they interact with conventional medicines, would help determine safety of their combined use.

Certain combinations may have advantageous interactions, increasing the efficacy or potency of the medicines and allowing for reduced dosages, thereby reducing potential toxicity. These combinations could assist in the development of new pharmaceutical formulations.

Sharing information

The WHO in its Traditional Medicine Strategy for 2014-2023 report emphasised the need for using traditional medicine to achieve increased healthcare.

Key role players from both systems of healthcare need to be able to share information freely.

The need for policy development is key. Both conventional and traditional medicine practitioners would need to be aware of and engage with patients on all the medicines they are taking.

Understanding the whole patient

Patients often seek treatment from both conventional and traditional sources, which can lead to side effects or duplication in medications.

A comprehensive understanding of a patient’s health profile makes care easier.

This could also prevent treatment failures, promote patient safety, prevent adverse interactions and minimise risks.

A harmonious healthcare landscape would combine the strengths of both systems to provide better healthcare for all.

Zelna Booth, Pharmacist and Academic Lecturer (Pharmacy Practice Division, Department of Pharmacy and Pharmacology, University of the Witwatersrand), University of the Witwatersrand

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

Source: The Conversation

Traditional Healers in Rural Mpumalanga Help Diagnose HIV

Photo by Sergey Mikheev on Unsplash

An initiative of Wits University’s MRC/Wits Agincourt Research Unit, the Traditional Healers Project convened two ‘open houses’ at local primary healthcare facilities – Rolle Clinic and Thulamahashe Community Health Centre in rural Bushbuckridge, Mpumalanga – in March 2023.

An ‘open house’ is a community and stakeholder gathering hosted at a public health facility in partnership with the Department of Health.

The aim of these sessions is to build on the relationship that the MRC/Wits Agincourt Research Unit has established between local traditional healers, community members, and healthcare facility staff to support the end of HIV through regular HIV counselling and testing.

Traditional healers in public health

The sessions supplement research that began almost a decade ago, which focuses on the role of traditional healers in healthcare access and delivery.

Specifically, this research aims to determine:

  • whether traditional healers can conduct HIV counselling and testing (HCT)
  • whether the patients of traditional healers are willing to undergo HCT that is administered by a traditional healer
  • whether traditional healers and biomedical healthcare workers can work together to help link patients to HIV/AIDS diagnosis and care.

The open house sessions form part of this research and provide a platform where traditional healers and biomedical healthcare workers can come together and build mutual understanding and trust, with a view to linking those who test positive for HIV with healthcare providers who can then administer lifesaving antiretroviral treatment (ART) and care.

15 traditional healers certified HIV counsellors and testers

The open houses drew an audience of more than 150 participants, including 15 traditional healers, local indunas [tribal chiefs], community healthcare workers (CHWs), community members, and representatives from Right to Care (a local collaborating partner on HIV) and the Department of Health.

Mr Wonderful Mabuza, Project Manager at the MRC/Wits Agincourt Research Unit, oversees the open houses and says that the successes to date have far surpassed expectations:

“It is exciting to be part of the group that is doing this work, knowing that we have a lot of people who visit traditional healers in our communities. It’s groundbreaking to have traditional healers trained to provide HIV counselling and testing – and amazing to see community members respond, with some never having tested previously.”

Gogo Singabeni, one of the 15 traditional healers who has completed the programme, says: “I was very excited to be invited to the HIV training, and that we would be certified in HIV testing and counselling. It’s important to show people proof that I am certified to do HIV testing.”

She adds: “The first day of testing [a patient] was very difficult for me. I was even shaking as I was conducting the test. I started with the first client, although I was shaking, and I managed to complete the process according to how we were trained. After the client left, I drew strength in seeing that I am able to do it.”

Partnerships imperative

Dr Ryan Wagner, Senior Research Fellow at the MRC/Wits Agincourt Research Unit, leads the traditional healers programme known collectively as Ntirhisano (Shangaan for ‘working together’).

He emphasises the importance of the Ntirhisano team, traditional healers, community healthcare workers, and the Department of Health collaborating to strengthen the referral system. 

“In order to expand coverage and increase uptake of HIV testing – and thereby contribute to ending new HIV cases – we need to embrace innovative approaches, such as traditional healer-initiated HIV counselling and testing,” says Wagner.

“We have recruited and trained 15 traditional healers in the Thulamahashe/Rolle area who, for the past six months, have been successfully testing their patients for HIV/AIDS. Those who tested positive have been referred to a local clinic or community healthcare worker.”

The Department of Health’s Primary Healthcare Supervisor, Sister Mariah Mkhari, says: “The Department of Health alone cannot do it, but with such collaborations between MRC/Wits and other stakeholders we will be able to conquer HIV. We welcome the initiative, and we hope Wits can expand to other areas in Bushbuckridge and train all traditional healers to test for HIV.”

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

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

Scientists Create Antidepressant Drug Candidates from Traditional African Plant Medicine

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

Native American Plant Remedies Found to Have Dual Properties

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