Bitter melon yields sweet results for diabetes
23 April 2008
Bitter melon is a popular vegetable used in Asian cooking and has long been an ingredient in traditional Chinese medicine. Now researchers have identified active ingredients in the warty green fruit that could lead to new treatments for diabetes.
'In many ancient Chinese medicine texts, bitter melon was described as being able to relieve fatigue and excess thirst, which are symptoms of diabetes,' explains Ye Yang, of the Chinese Academy of Sciences' Shanghai Institute of Materia Medica.
Researchers have shown that bitter melon extract can reduce blood sugar levels in animals and humans - important in the control of diabetes, where blood sugar levels can get dangerously high. But little is known about which chemicals in the vegetable give rise to its beneficial effects. 'That's where our research comes in,' says Ye's Sydney-based collaborator Nigel Turner, of the Garvan Institute at the University of New South Wales.
Active ingredients from bitter melon could lead to new diabetes drugs
In a study recently published in Chemistry & Biology, Ye and colleagues tested different fractions of bitter melon, also known as bitter gourd, for their ability to attract glucose transporters to the surface of muscle and fat cells - a crucial step in the uptake of sugar from the blood by tissues.
The team found that fractions containing cucurbitane triterpenoids had the most powerful effect on the tissues and identified four novel cucurbitane glycosides and a karaviloside that were responsible for the activity. The five molecules seem to work by boosting the levels of an enzyme called adenosine monophosphate-activated protein kinase (AMPK), a key regulator of glucose uptake.
After pulping a tonne of bitter melon, the researchers were able to get enough of two of the cucurbitane glycosides for animal studies. They found that these two compounds markedly increased the rate of fat oxidation, which is often impaired in diabetic patients, and also boosted the speed with which both normal mice and mice with diabetes cleared injected glucose from their bloodstream.
'This is the first time that cucurbitane triterpenoids have been unequivocally implicated in regulation of glucose transport and antidiabetic activities,' says Ye. 'They may provide novel drug leads for treating diabetes and obesity.'
'It's a very interesting study,' says David Moller, vice president of the division of endocrine and cardiovascular research and clinical investigation at Lilly Research Laboratories in Indianapolis, Indiana, US. 'The potency of those molecules is particularly impressive.' He says that most plant-derived compounds characterised to date have had anti-diabetic effects at micro- or milli-molar concentrations, whereas some of the cucurbitane triterpenoids isolated from bitter melon are effective at doses as low as 10 nanomolar.
The findings could spark a new wave of drug discovery homing in on AMPK, an area of research that has been on a standstill for lack of potent activators, Moller adds. Most diabetes drugs on the market that target AMPK have only moderate effects and are associated with serious side effects.
Turner agrees. 'Cucurbitane triterpenoids may be a more promising remedy as they are naturally derived and have a potent effect at much lower doses than existing drugs,' he notes.
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M-J Tan et al, Chem. & Biol., 2008, 15, 263 (DOI: 10.1016/j.chembiol.2008.01.013)
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