A compound called rutin (see structure - a quercetin derivative), commonly found in fruits and vegetables and
sold over the counter a dietary supplement, has been shown to inhibit
the formation of blood clots in an animal model of thrombosis.
As per the researchers claim,
"Approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke."..
The study focused on protein disulfide isomerase (PDI) which is found
in all cells. Investigators in BIDMC's Division of Hemostasis and
Thrombosis had previously shown that PDI is rapidly secreted from both
platelets and endothelial cells during thrombosis, when a clot forms in a
blood vessel, and that inhibition of PDI could block thrombosis 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," says
Flaumenhaft. However, because intracellular PDI is necessary for the
proper synthesis of proteins, the scientists had to identify a specific
compound that could block the thrombosis-causing extracellular PDI --
without inhibiting the intracellular PDI.
They began by conducting a high-throughput screen of a wide array of
compounds to identify PDI inhibitors. Among the more than 5,000
compounds that were screened, quercetin-3-rutinoside (rutin) emerged as
the most potent agent. "Rutin was essentially the champion compound,"
says Flaumenhaft.
A bioflavonoid that is naturally found in many fruits, vegetables and
teas including onions, apples and citrus fruits, rutin is also sold as
an herbal supplement, having received a special designation for safety
from the U.S. Food and Drug Administration (FDA). Surprisingly, studies
of the rutin molecule demonstrated that the same part of the molecule
that provides rutin with its ability to inhibit PDI also prevents the
compound from entering cells."That finding explained how this compound
can be both a potent inhibitor of PDI and a safe food supplement," says
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.
Because they knew that humans would be taking rutin in pill form, they
included studies in which the compound was administered orally and
determined that it successfully retained its anti-thrombotic properties
when it was metabolized following oral ingestion.
"Rutin proved to be the most potently anti-thrombotic compound that
we ever tested in this model," says Flaumenhaft. Of particular note,
rutin was shown to inhibit both platelet accumulation and fibrin
generation during thrombus formation. "Clots occur in both arteries and
in veins," explains Flaumenhaft. "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."
Even with the use of existing anti-clotting therapies, such as
aspirin, clopidogrel (Plavix) and warfarin (Coumadin), each year there
are approximately 400,000 recurrent episodes among patients who
previously experienced a stroke or heart attack, says Flaumenhaft.
"A safe and inexpensive drug that could reduce recurrent clots could help save thousands of lives," he adds. "These pre-clinical trials provide proof-of-principle that PDI is an important therapeutic target for anti-thrombotic therapy, and because the FDA has already established that rutin is safe, we are poised to expeditiously test this idea in a clinical trial, without the time and expense required to establish the safety of a new drug."
Ref 1. http://www.jci.org/articles/view/61228
2. http://www.bidmc.org/News/InResearch/2012/May/Rutin_BloodClots.aspx