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Cardiovascular Medicine

Potent, Natural Anti-Clotting Agent Found
Neil Wagner

July 14, 2012

A plant pigment found in fruits, vegetables, buckwheat, tea and other foods may be the blood clot prevention drug of the future. And the future may not be too far away.

Rutin is a flavonoid, a plant pigment with anti-oxidative properties. It's already sold as a dietary supplement, though pregnant and breast-feeding women should not take it. Rutin is thought to possibly strengthen capillaries and reduce inflammation.

In a recent study at Harvard Medical School, rutin emerged as the champion compound of over 5,000 tested at blocking a key step in blood clot formation. Blood clot formation is a multi-step process, sometimes called a cascade. If you block just one step in the sequence, clots do not form.

About half of all deaths are due to a blood clot in the brain or in the heart, which cause strokes or heart attacks. So there's plenty of need for a safe and effective anti-clotting drug. Among the drugs currently used, warfarin (coumadin) in particular can be a very high-risk medication.

The study was looking for compounds that could inhibit (block) an enzyme called protein disulfide isomerase (PDI). This enzyme is found in all types of cells and is rapidly released by platelets and endothelial cells (the cells that line the inner walls of blood vessels) during blood clot formation. Inhibition of PDI had been previously shown to block blood clot formation in mice.

But just inhibiting PDI won't be very helpful, because the PDI inside of cells has several important metabolic functions. To be useful, a PDI inhibitor would have to inhibit PDI outside of cells, in the bloodstream for example, but not inside of blood cells or other cells. Rutin can do this because it is not taken up by cells--it remains in the bloodstream.

In addition to testing rutin's ability to inhibit PDI in the laboratory, the researchers also tested the ability of oral rutin to inhibit blood clot formation in mice. Not only was rutin effective, it was effective at concentrations that are well tolerated in mice and humans.

Blood clots form in arteries by a slightly different process than they do in veins. Arterial clots are rich in platelets, while venous clots have few platelets but are rich in the compound fibrin. Clot prevention strategies in arteries and veins often use different medications, with some arterial medications focused on blocking platelet accumulation, while venous medications often focus on blocking steps in the clotting cascade, often the generation of fibrin. In the current study, rutin inhibited both platelet accumulation and fibrin generation, suggesting that it may be helpful in preventing both arterial and venous clots.

There's no word yet on when clinical tests of rutin will begin. The fact that rutin is already known to have little or no toxicity in humans should help speed the trial process along.

An article on the study was published online by the Journal of Clinical Investigation.