Physician-scientist Barry Paw (second from left) with members of his lab.

Iron is an essential element for life. Red blood cells rely on it to create the protein required to transport oxygen in our body. Iron is shuttled to the right places in the body through an elaborate series of reactions and processes, but when that system fails, it can cause diseases.

Drawing from a natural substance found in the wood of certain species of trees, BWH researchers recently identified a compound that can correct iron-delivery defects in preclinical models. The compound, known as hinokitiol, is described in a paper published this month in Science.

The study, done in collaboration with scientists at University of Illinois Champaign-Urbana, lays the groundwork for investigating hinokitiol’s full potential beyond cellular and model organisms, possibly one day in humans. If successful, these findings may lead to novel therapies for diseases such as iron deficiency anemia (too little iron), hemochromatosis (too much) or sideroblastic anemia (too much in the wrong part of a cell).

“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 the Division of Hematology. “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 studied the properties of hinokitiol in yeast, mouse red blood cells and zebrafish models, all of which lacked the ability to transport iron. When the team administered hinokitiol in these preclinical models, they found that it corrected the 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 hinokitiol that can mimic the biological function of a missing protein may have potential for treating human diseases.