Automated Method #World Research Awards...

 Automated Method Provides a “Snapshot” of a Plant’s Metabolic Effects


Scientists developed a new way to help understand what happens in the body when people consume a plant product and the many chemicals it contains. The American Chemical Society’s Journal of Natural Products published the method to quickly analyze the effects of a natural product, developed at Emory University.

As a test case, the paper focused on biotransformation of chemicals from the kratom plant by human liver cells in a laboratory dish. The researchers developed an automated method - based on high-resolution mass spectrometry and molecular network mapping - to gain a detailed, big-picture view of the resulting metabolites, or chemicals produced.

The new, streamlined methodology can be broadly applied to nutrition and dietary supplement research, filling a critical gap in the field.

“Plants evolved extraordinarily complex chemical defenses and signaling systems,” says Cassandra Quave, co-senior author of the study and professor of dermatology at Emory School of Medicine and the Center for the Study of Human Health. “Our new approach in molecular mapping gives us a way to follow how that chemical complexity is reshaped by human metabolism.”

“Our technique does not just look at how one compound in this plant is metabolized,” adds William Crandall, first author of the study and a PhD student of molecular and systems pharmacology in Emory’s Laney Graduate School. “It shows how dozens of compounds are metabolized at one time.”

“This method marks a major, transformative step in natural products research,” says Dean Jones, co-senior author of the paper and professor in Emory School of Medicine. “A process that used to require years of work now takes just days.”

The new framework provides a starting point to help standardize and deepen understanding of the effects of a natural product when it is consumed in a manner typical to traditional medicine, such as leaves brewed for a tea.

The breakthrough was driven by the passion and dedication of Crandall, who plans a career in natural products research, combined with the unique resources of his co-mentors, Quave and Jones. “All these factors came together,” Jones says. “You can call it serendipity.”

Quave is a leading ethnobotanist, studying how plants are used as medicine in traditional cultures. She has built a natural product library of more than 3,000 extracts isolated from plants, including documentation of the medicinal uses of the plants. Her lab has discovered the actual mechanisms for how some of these natural products work on dangerous pathogens, including antibiotic-resistant bacteria.

Jones, professor of medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, is director of the Emory Clinical Biomarkers Laboratory. He is a world leader in the development of high-resolution techniques for metabolomic analyses of nutritional and environmental factors in human health and disease.

Crandall enjoys tapping cutting-edge technology to explore the ancient secrets of plants. “I love the complexity and the endless possibilities of all the compounds in plants,” he says. “There are always more interesting things hidden way down in the weeds just waiting to be discovered.”

Around half of modern-day medicines trace their origins to a natural product - a chemical compound produced by a living organism such as a plant, animal or bacteria. Common examples include aspirin (based on a pain-relieving compound found in willow bark) and Taxol (a potent anti-cancer drug derived from the bark of the Pacific yew tree).

Plants are master chemists - a single species may produce hundreds or thousands of chemicals to help the plant function normally and defend itself from predators and diseases. The richness of this treasure trove, however, makes it challenging to research.

“Science is typically reductionist,” Crandall explains. “You approach a large system, like a medicinal plant, and you try to isolate a compound responsible for that medicinal activity.”

The problem with that approach, he adds, is it doesn’t consider all the interactions of the many different chemicals of a plant when it is consumed.


Despite the enormity of the challenge, Crandall worked to find a streamlined solution to this complex problem.

He chose kratom (Mitragyna speciosa) as his test subject due to the extensive research available on the plant and its active ingredients.

A plant from the coffee family native to Southeast Asia, kratom has deep roots in herbal medicine due to its reported mood-enhancing, pain-relieving effects. It is traditionally consumed by chewing the leaves or brewing them in water to drink as a tea.

Modern-day science isolated two major psychoactive ingredients in kratom: alkaloids with opiate-like effects known as mitragynine and 7-hydroxmytragynine.

In the United States, kratom leaves and products prepared using these active ingredients are sold as extracts, pills, capsules and suspensions. Kratom is often used to self-treat conditions such as pain, coughing, diarrhea, anxiety and depression, opioid-use disorder and opioid withdrawal, according to the U.S. Food and Drug Administration (FDA).


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