Team at Colorado State Makes Standardized Pick-Me-Up Extract of Saint-John’s-Wort Easier to Produce with Fewer Side Effects

A group of researchers at Colorado State University has unlocked a method to easily mass produce the mood-lifting compound in Saint-John’s-wort, which would make standardized extracts easier to produce while eliminating potentially harmful side effects of other chemicals in the herb.

Saint-John’s-wort, which can’t be grown in the United States because of its noxious weed status, is imported from Europe. It is widely known for its antidepressant qualities but also is linked to successful anti-cancer and anti-HIV research. The anti-depressant chemical that the herb contains, called hypericin, is present in the leaf of the plant. But the leaf also contains additional chemicals that have been known to counteract other medications, such as heart medications, birth control pills and blood-pressure regulators.

"This innovative method provides a purified, cost-effective extract which can be produced in the United States. The extract produced under these conditions should decrease or eliminate the adverse drug interactions that Saint-John’s-wort may currently cause," said Jorge Vivanco, lead researcher on the team and Colorado State University assistant professor in the Department of Horticulture and Landscape Architecture. "Hypericin can now be produced in large, isolated quantities in a process that is similar to how antibiotics are produced today."  

Saint-John’s-wort is one of the most popular herbal remedies available to consumers today and is commonly used to counter mild depression. However, like all herbal remedies, it is not monitored by the Food and Drug Administration, which means that the quality of each pill, even those in the same bottle or produced by the same company, may not contain the same amount of the herb and may also contain other harmful chemicals. Because they are not regulated, herbal products vary greatly as to their chemical composition and quality. Saint-John’s-wort also interacts with certain drugs, and these interactions can be dangerous, according to the National Institutes of Health.  

The red color of hypericin proved key to the Colorado State research team’s ability to make reproducing it so simple, according to the researchers. The group, comprised of experts who worked collaboratively from three different departments within the university, looked for precursors, or enzymes, that help form the compound hypericin within Saint-John’s-wort. Emodin is a precursor to hypericin; when two molecules of emodin bond in a process involving an enzyme, hypericin is formed.  

Emodin is a yellow-colored molecule, but hypericin is a bright red compound, which makes it easy to identify. The group of researchers isolated each gene of Saint-John’s-wort and inserted the individual genes into E. coli bacteria, which was used to quickly produce cells. The bacteria holding Saint-John’s-wort genes grew in plates containing emodin. The bacteria that contained the correct combination of emodin and Saint-John’s-wort genes that trigger the production of hypericin actually produced hypericin cells in the laboratory that turned red.

In theory, each "colony," or group, of E. coli cells in these conditions contains one gene from the plant. This approach allowed the researchers to quickly isolate the specific gene involved, called hyp-n, from the plant that is involved in hypericin production. More typical approaches to isolate genes and enzymes in Saint-John’s-wort and track their role in molecule production can take years.

Of the 50,000 cell colonies in the test, just eight turned red, indicating that the gene in that colony had a role in creating hypericin. The genes in each of those colonies were expressed, and the compound was grown in larger quantities. This method makes it possible for hypericin to be grown in large, artificial systems similar to how antibiotics are produced.  

Little has been known to date about how hypericin is produced, including the enzymes or genes that initiated its production.  

In addition to Vivanco, team members included Harsh Pal Bais and Ramarao Vepachedu, post-doctoral researchers in Colorado State’s Department of Horticulture and Landscape Architecture; Chris Lawrence, Colorado State Department of Bioagricultural Sciences and Pest Management assistant professor; and Frank Stermitz, Department of Chemistry professor. Research for this project was funded by the Colorado State University Agricultural Experiment Station, National Science Foundation and the Colorado State Invasive Weeds Initiative.