Dr. Benedict Kolber (third from right) poses with colleagues Dr. Télesphore Nguelefack (second from left) and Dr. Kevin Tidgewell (fourth from right), and faculty from the Higher Teacher Training College University of Yaounde 1 Department of Chemistry.
For millennia, people around the world have relied on various plant extracts as medicine. As the quest continues for non-opioid pain-relief medications, a University of Texas at Dallas researcher is spearheading an international collaboration to learn which natural remedies work and why.
Inspired in part by a college immersion experience in Cameroon 25 years ago, neuroscientist Dr. Benedict Kolber has allied with researchers in the African nation to discover the most beneficial compounds used there in traditional treatments.
Kolber, the Dean Bert Moore Distinguished Professor of neuroscience in the School of Behavioral and Brain Sciences and in the Center for Advanced Pain Studies, described his first time in Cameroon building wells, pumps and bridges for a nongovernmental organization as “an amazing, transformative experience” that led him to envision going back someday.
More than a decade later, at a scientific conference in Tokyo, he noticed a poster showing the flags of nations represented at the event, including Cameroon.
“That was rare, because there’s not a lot of resources for international travel in Cameroon,” he said. “I decided that I had to find this person.”
An inverted fluorescent microscope at the University of Dschang is used to phenotype mice that express green fluorescent proteins in neurons.
Dr. Benedict Kolber works with Cameroonian and Senegalese PhD students to harvest dorsal root ganglion neurons for in vitro calcium imaging experiments.
Kolber met Dr. Télesphore Nguelefack, a professor of physiology and pharmacology at the University of Dschang who studies traditional medicine. Nguelefack collects evidence that traditional medicine applications are not simply placebos, and he seeks ways to make them more potent.
Traditional medicine, as defined by the World Health Organization, comprises practices, skills, knowledge and philosophies originating in different historical and cultural contexts that predate biomedicine and that emphasize nature-based remedies and holistic approaches.
“Nguelefack was asking people in rural areas what they do for arthritis or stomach pain,” Kolber said. “These conversations yielded a range of tree barks, leaves and berries that are made into teas, tinctures and more.”
Nguelefack tested the traditional medicines using animal models to rule out the placebo effect and found a beneficial effect in more than 60% of his experiments. But the Cameroonian lacked the resources to isolate and test specific compounds or extracts. Kolber saw an opportunity to collaborate.
“I realized we could build on his efforts,” he said. “I wrote a grant proposal with my colleague, medicinal chemist Dr. Kevin Tidgewell at the University of Kentucky College of Pharmacy to go to Cameroon.”
In one of his expeditions, Kolber connected with a traditional healer in the southeastern rain forests of Cameroon from the Baka ethnic group. He showed native and foreign scientists the sources of some of his cures.
“He’d say things like, ‘See that tree over there? We collect that only in January, and only if we see ants on the tree.’ Partnering with people who can share all these things that they and their ancestors have done is uniquely useful,” Kolber said.
The arrangement they created has Cameroonian scientists performing initial screenings, then sending extracts to Kolber’s and Tidgewell’s labs, where compounds from those extracts are identified and tested. They send pure compounds back to Cameroon for final evaluation.
“In our most recent journal article, for instance, we took a raw extract that had an analgesic effect and looked at its individual components to see how the effect changed depending on what we removed,” Kolber said. “When you isolate compounds, you can often find an additional effect, positive or negative.”
The International Association for the Study of Pain funded several years of collaboration. The team subsequently received a two-year grant (R21TW012825) from the National Institutes of Health’s National Center for Complementary and Integrative Health and the Fogarty International Center, also part of the NIH.
“This funding has supported publication of four of our research papers,” Kolber said. “We’ve traveled to Cameroon twice, bringing in researchers from around Central Africa for training. We’re hoping to build multiple collaborations so that the next iteration of this project will expand around the country.”
“We’ve traveled to Cameroon twice, bringing in researchers from around Central Africa for training. We’re hoping to build multiple collaborations so that the next iteration of this project will expand around the country.”
Dr. Benedict Kolber, the Dean Bert Moore Distinguished Professor of neuroscience in the School of Behavioral and Brain Sciences
In July, Kolber, Tidgewell and their Cameroonian colleagues published a study in the Journal of Ethnopharmacology detailing their analysis of the extracts from a soapberry shrub called Paullinia pinnata used to treat arthritis. They found that the extracts caused noticeable relief from pain, inflammation and edema in rodents, and that exposure to one extract reduced firing of isolated human pain neurons. The researchers used a technique called liquid chromatography-tandem mass spectrometry to identify eight potentially active compounds in the extracts.
The team published another study in August in the American Chemical Society journal ACS Omega about bioactive metabolites from Acacia sieberiana, a large tree known as the paperbark thorn. Researchers extracted from the plant a chemical called moupinamide, which is known to be an antioxidant. It showed promising pain relief results in rodent models without dangerous side effects. They then tested moupinamide on lab-grown human pain neurons and found it also reduced firing of those neurons, possibly by affecting voltage-gated sodium channels in the cells.
From left: Dr. Benedict Kolber, Dr. Télesphore Nguelefack and Dr. Kevin Tidgewell pose in front of a tree that has been sampled by traditional healers in the Dja Faunal Reserve, a UNESCO World Heritage site.
The NIH funding also supports efforts to enable Cameroonian scientists to perform as much of the work as possible locally by building up capabilities and infrastructure.
“In exchange, we may expand access to an incredible natural resource used for thousands of years,” Kolber said. “If we can leverage traditional remedies to create new nonaddictive pain drugs, it’s worth it for all of us.”
Kolber emphasized that collaborating with partners in Cameroon as equals is crucial for the project to succeed.
“With the history of colonization and resource removal from Africa, there can absolutely be distrust,” he said. “We have written agreements that outline who owns the intellectual property. We need to sustain these fundamental international conversations.”
Many of the compounds they identify have been described structurally before but have no reported use.
“We hope to find a known compound that can be modified easily, with qualities favorable from a medicinal chemistry perspective,” Kolber said. “That would be a great starting point for creating a new drug.”
Kolber said the potential for traditional remedies to impact lives already has been established in mainstream medicine.
“Opiates are from the poppy plant; aspirin derives from the bark of the willow tree,” he said. “Even in the U.S., we use Echinacea, ginger root, curcumin and so many natural products. Ginseng, fish oil, omega-3 and turmeric — the list goes on. We’re performing rigorous scientific investigation of traditional medicine because there are many untapped opportunities here to learn what works.”
Source: news.utdallas.edu
