Research outlines biochemistry of xanthohumol as avenue to treat metabolic syndrome

Researchers at Oregon State University (OSU) have identified for the first time more precisely how xanthohumol works, and why it may have promise in addressing the high cholesterol, blood sugar, obesity and other issues that are collectively referred to as "metabolic syndrome."

Published in the professional journal BBA - Proteins and Proteomics and claimed by the researchers to be a fundamental advance in understanding the compound found in hops, the findings are expected to help prevent or treat the lipid and metabolic disorders that are a primary killer of people in the developed world, as more than 25 percent of the adults in the United States meet the criteria for metabolic syndrome.

The syndrome, which puts people at significantly increased risk for cardiovascular disease and type-2 diabetes, is defined by diagnosis of three or more of several conditions, including abdominal obesity, elevated lipids, high blood pressure, pro-inflammatory state, a pro-thrombotic state and insulin resistance or impaired glucose tolerance.

Based on mass spectrometry in combination with a chemical labeling technique, OSU researchers concluded that several "prenylflavonoids," particularly xanthohumol, clearly are a ligand, or have a binding mechanism that promotes the activity of the Farnesoid X Receptor, or FXR. FXR, in turn, is a master regulator of lipid and glucose metabolism, namely the body's processing of fats and sugar.

"There's already interest in targeting FXR as a possible approach to a therapy for fatty liver disease, type2 diabetes and obesity," Claudia Maier, a professor of chemistry in the OSU College of Agricultural Sciences, was quoted as saying in a news release from OSU on Monday. "With this work we've identified a unique binding mechanism and chemical structure that could make that possible. This is really very interesting, and very promising."

This new understanding of the FXR receptor at the molecular level, the researchers said, could, in theory, facilitate the use of compounds that take advantage of it, such as xanthohumol, or development of other compounds with a similar chemical structure that work even better. "We now see how these prenylflavonoids are working, and with modification through computational approaches it might be possible to even improve upon that," said Liping Yang, the lead author on the study and faculty research assistant in the OSU Department of Chemistry.

"The end result might be either supplements or a prescription drug, with the potential to address metabolic syndrome, non-alcoholic liver disease, diabetes and other metabolic disorders," noted Yang.

The FXR receptor is a part of normal lipid and glucose metabolism, working in collaboration with appropriate diet, weight, exercise and other healthy activities. However, its function can be eroded by intake of too much fat and sugar. Restoring that function may help address metabolic problems.

In previous research, published earlier this year by OSU researchers Cristobal Miranda and Fred Stevens, laboratory animals on a high-fat diet and a high dosage of xanthohumol showed their LDL, or "bad" cholesterol reduced by 80 percent; their insulin level down by 42 percent; and their level of IL-6, a biomarker of inflammation, by 78 percent. And weight gain was also constrained, compared to animals not given xanthohumol. Endit