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Two compounds found in red grapes and oranges combined could treat diseases
· Researchers are hoping pharmaceutical companies will use new compound combination in breakthrough drugs
A combination of two compounds found in red grapes and oranges could
be used to improve the health of people with diabetes, and reduce cases
of obesity and heart disease.
The find has been made by University of Warwick researchers who now
hope that their discovery will be developed to provide a treatment for
patients.
Professor Thornalley who led research said: “This is an incredibly
exciting development and could have a massive impact on our ability to
treat these diseases. As well as helping to treat diabetes and heart
disease it could defuse the obesity time bomb.”
The research ‘Improved glycemic control and vascular function in
overweight and obese subjects by glyoxalase 1 inducer formulation’ has
been published in the journal Diabetes, and received funding from the
UK’s innovation agency, Innovate UK. The project was a collaboration
between the University of Warwick and University Hospitals Coventry and
Warwickshire (UHCW) NHS Trust.
A team led by Paul Thornalley, Professor in Systems Biology at
Warwick Medical School, studied two compounds found in fruits but not
usually found together. The compounds are trans-resveratrol (tRES) –
found in red grapes, and hesperetin (HESP) – found in oranges. When
given jointly at pharmaceutical doses the compounds acted in tandem to
decrease blood glucose, improve the action of insulin and improve the
health of arteries.
The compounds act by increasing a protein called glyoxalase 1 (Glo1)
in the body which neutralises a damaging sugar-derived compound called
methylglyoxal (MG). MG is a major contributor to the damaging effects of
sugar. Increased MG accumulation with a high energy diet intake is a
driver of insulin resistance leading to type 2 diabetes, and also
damages blood vessels and impairs handling of cholesterol associated
with increased risk of cardiovascular diseases. Blocking MG improved
health in overweight and obese people and will likely help patients with
diabetes and high risk of cardiovascular disease too. It has already
been proven experimentally that blocking MG improves health impairment
in obesity and type 1 and type 2 diabetes.
Although the same compounds are found naturally in some fruits, the
amounts and type required for health improvement cannot be obtained from
increased fruit consumption. The compounds that increase Glo1 and are
called a ‘Glo1 inducer’. Pharmaceutical doses for patients with obesity,
diabetes and high risk of heart disease could be given to patients in
capsule form.
Professor Thornalley increased Glo1 expression in cell culture. He
then tested the formulation in a randomised, placebo-controlled
crossover clinical trial.
Thirty-two overweight and obese people within the 18-80 age range who
had a BMI between 25-40 took part in the trial. They were given the
supplement in capsule form once a day for eight weeks. They were asked
to maintain their usual diet and their food intake was monitored via a
dietary questionnaire and they were also asked not to alter their daily
physical activity. Changes to their sugar levels were assessed by blood
samples, artery health measured by artery wall flexibility and other
assessments by analysis of blood markers.
The team found that the highly overweight subjects who had BMIs of
over 27.5 with treatment displayed increased Glo1 activity, decreased
glucose levels, improved working of insulin, improved artery function
and decreased blood vessel inflammation. There was no effect of placebo.
Professor Thornalley said: “Obesity, type 2 diabetes and
cardiovascular disease are at epidemic levels in Westernised countries.
Glo1 deficiency has been identified as a driver of health problems in
obesity, diabetes and cardiovascular disease.”
“Diabetic kidney disease will be the initial target to prove
effective treatment for which we are currently seeking commercial
investors and partners. Our new pharmaceutical is safe and expected to
be an effective add-on treatment taken with current therapy.
“The key steps to discovery were to focus on increasing Glo1 and then
to combine tRES and HESP together in the formulation for effective
treatment.
“As exciting as our breakthrough is it is important to stress that
physical activity, diet, other lifestyle factors and current treatments
should be adhered to.”
Professor Martin O Weickert, Consultant in Diabetes and Endocrinology
at UHCW NHS Trust, and co-applicant for the grant, said: “We were
really excited to participate in this study with Warwick Medical School,
as taking part in world-leading research makes a real difference to our
patients both now and in the future.
“As well as the positive effects for the UHCW patients who took part
in the trial, we hope this study will lead to new treatments to help
patients with diabetes and cardiovascular diseases all over the world.”
Prof. Thornalley and his team are now hoping manufacturers will want
to explore the use of the compound as pharmaceutical products.
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