The study – published in the Journal of Clinical Investigation – reveals that the compound that is commonly found in fruits and vegetables in addition to being sold as a dietary supplement, could have promise in blocking the formation of blood clots in an animal model of clotting (thrombosis).
Led by Robert Flaumenhaft of Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School, the researchers identified the ‘popular flavonoid’ quercetin-3-rutinoside (rutin) as having possible benefits for the prevention and treatment of stroke and heart attack, as well as deep venous thrombosis (DVT) and pulmonary embolism.
"Rutin proved to be the most potently anti-thrombotic compound that we ever tested in this model," said Flaumenhaft. In particular, he revealed that rutin was shown to inhibit both platelet accumulation and fibrin generation during clot (thrombus) formation.
"Clots occur in both arteries and in veins," he explained. "Clots in arteries are platelet-rich, while those in veins are fibrin-rich. This discovery suggests that a single agent can treat and prevent both types of clots."
Rutin is naturally found in many fruits, vegetables and teas including onions, apples and citrus fruits, rutin is also sold as an herbal supplement. The Harvard expert added that because the US Food and Drug Administration has already established that rutin is safe, the team are now ‘poised’ to test the idea in a clinical trial.
The new study focused on protein disulfide isomerase (PDI) which is found in all cells. The researchers noted that previous work has shown that PDI is rapidly secreted from both platelets and endothelial cells during thrombosis – and that inhibition of PDI could block clotting in a mouse model.
"This was a transformative and unanticipated finding because it identified, for the first time, that PDI is secreted from cells in a live animal and is a potential target for preventing thrombosis," said Flaumenhaft.
However, he noted that because intracellular PDI is necessary for the proper synthesis of proteins, researchers had to then identify a specific compound that could block the clot-causing extracellular PDI – without blocking PDI in cells.
The team began by conducting a high-throughput screen of a wide array of compounds to identify PDI inhibitors. From more than 5,000 compounds that were screened, rutin emerged as the most potent agent.
"Rutin was essentially the champion compound," said Flaumenhaft.
The team added that further study of the rutin molecule revealed that the same part of the molecule that provides the compound with its ability to inhibit PDI also prevents it from entering cells.
"That finding explained how this compound can be both a potent inhibitor of PDI and a safe food supplement," said Flaumenhaft. "Our next questions were, 'Is this compound anti-thrombotic? Can it prevent blood clots?'"
The team went on to test rutin in a mouse model of thrombosis – finding that it successfully retained its anti-clotting properties when it was metabolised following oral ingestion.
Source: Journal of Clinical Investigation
Published online ahead of print, doi: 10.1172/JCI61228
“Protein disulfide isomerase inhibitors constitute a new class of antithrombotic agents”
Authors: R. Jasuja, F.H. Passam, D.R. Kennedy, S.H. Kim, L. van Hessem, et al