Compound corrects iron-delivery defects

"The long-term therapeutic implications of our work with Hinokitiol points to potentially using this chemical to correct anemias caused by genetic deficiencies of iron transporters required for normal red cell formation," said co-corresponding author Barry Paw, MD, PhD, of BWH's Division of Hematology. "At the same time, Hinokitiol has the potential to correct iron-overload syndromes, such as hemochromatosis. More extensive clinical trials are necessary to work out the full potential of Hinokitiol and to identify potential toxicities that we have not identified using preclinical models."

Hinokitiol is a natural product found in the wood of trees. Originally isolated from the Taiwanese hinoki tree, this small molecule is also found in cedar wood.

The research team initially studied the properties of Hinokitiol in yeast -- a classic model organism for studying biological processes, such as iron transport, that have been conserved across evolution. Collaborators at University of Illinois found that the compound could transport iron across the yeast cellular membrane in mutant yeasts lacking their major iron uptake transporters. BWH investigators provided mouse erythroid (red) blood cells as well as zebrafish mutants, both of which lacked the ability to transport iron. When the team administered Hinokitiol in these models as well as rodent models, they found that it remedied the blocked iron on the outside of the cells, or subcellular organelles, correcting anemia at the cellular level.

"We found that Hinokitiol can restore iron transport within cells, out of cells or both," said Paw. "It can also promote iron gut absorption and the creation of hemoglobin in some of our models. These findings suggest that small molecules like Hinkitiol that can mimic the biological function of a missing protein may have potential for treating human diseases."