Researchers Getting Closer in Using Beer Hops to Fight Disease

21 Mar 2016 --- Research presented at a meeting of the American Chemical Society (ACS) reports that scientists are close to synthesizing healthful hops compounds in the lab.

Hops, the cone-shaped buds that give beer its bitter flavor, may provide a surprisingly healthful punch. They have been widely studied for their ability to halt bacterial growth and disease. Now, researchers say this advance could one day help scientists create medicines from these compounds without having to extract them from plants.

The researchers presented their work at the 251st National Meeting & Exposition of the ACS, the world’s largest scientific society.

“We certainly do not suggest drinking beer as medicine!” Kristopher Waynant, Ph.D., who leads the project, told NutritionInsight.

“When researchers extract healthful chemicals from hops, they first have to determine whether they have separated out the specific compounds they’re interested in. But if you can figure out how to make these compounds from scratch, you know they are the right ones.”

The compounds Waynant is interested in are humulones, which are alpha acids that have anti-cancer and anti-inflammatory properties, and lupulones, which are beta acids that have equally important but not as well-understood biological effects.

“Humulones and lupulones (alpha and beta acids, respectively) are compounds found in the soft resin material of female hop cones. Hops have been used in beer brewing for 1000’s of years. During wort boiling, in the beer brewing process, the alpha acids isomerize to isohumulones (cis and trans) which are the main bittering agents in beer,” Waynant explained.

Scientists ultimately want to harness these activities to potentially improve human health. But before humulones and lupulones can be turned into effective pharmaceuticals, scientists must confirm that they are extracting the proper acids from hops. In theory, they can do this by separating the acids with high performance liquid chromatography (HPLC), but results from this method need to be compared to analytical standards, which do not yet exist for the individual compounds.

“Just because a natural compound is biologically active, doesn’t mean it will be a great medicine,“ Waynant clarified.

In order to create a library of such analytical standards, Waynant and undergraduate student Lucas Sass, both at the University of Idaho, are attempting to synthesize a set of humulones and lupulones in the lab. Waynant said: “We are using known chemistries to start a library of humulones and lupulones to create a series of (potentially) more biologically active compounds.“

“The other natural humulone analogs we are interested in are (-)-cohumulone and (-)adhumulone. Adhumulone has a 2nd undetermined stereocenter that we hope to specify. Through this synthetic strategy we can potentially provide standards for the analytics of alpha and beta acids for the brewing industry. In conjunction with the natural humulones, we are interested in developing our synthetic strategy as to see if we can efficiently develop a diverse (but small) library of humulone analogs to further test for biological activities.”

The researchers start with phloroglucinol — a commercially available compound that is derived from plants. So far, they have been developing multi-step processes to synthesize three types of humulones. They begin with acylation and prenylation steps, and then use transition-metal catalysis with a chiral ligand to create asymmetric products. The team is still working on tweaking the final step of converting the intermediate products in the desired humulones efficiently.

“Unfortunately, the first few pathways I proposed were not the best or most efficient,” Waynant admits. “But Lucas has gone through the literature and analyzed different ways to perform each of these steps to get the best results.”

Currently, Sass is making progress on optimizing the first two steps. “It’s been a lot of trial and error,” Sass says. “But it’s so exciting when an approach finally works.”

The researchers say they are getting very close to optimizing the complete method for producing humulones in the lab.
“As this project is still in its infancy we have yet to produce a natural humulone or a new humulone derivative. However, we have been working hard on the process and its scalability. We hope to have humulones available for testing in the near future.” Waynant explained.

In the future, Waynant’s team will continue the project to synthesize a broader range of humulones and lupulones. He also plans to reach out to and collaborate with biologists and medical researchers to develop active agents for pharmaceuticals to treat cancers or inflammatory diseases from these beer-inspired compounds.

“Hop extracts (as well as isolated humulones and lupulones) have already shown a wide variety of health benefits. Many studies have shown that these compounds or extracts possess anti-inflammatory, anti-cancer activity (mostly in vitro), COX-2 inhibition, in addition to their well-documented antibacterial properties. I am also aware of a company in Seattle (Kindex pharmaceuticals) that is using an isomerized humulone in phase 2 murine models towards a diabetes drug.”

NutritionInsight asked how this research will affect different industries: “Our work will not affect the food industry at all,” Wayant replied. “We are not starting from isolated humulones or lupulones. Our work may not benefit the hop industry except, of course, to display the biological activities of the natural compounds found in hops.”

“As for cooking them [to make hop-containing food products], I would imagine that the humulones would certainly isomerize as they do in the wort boiling process to the isohumulones (the main bittering agents),” Waynant concluded.

The researchers acknowledge funding from the University of Idaho and the National Institutes of Health IDeA Networks of Biomedical Research Excellence program.

by Kerina Tull