Identifying new agents for lowering blood glucose levels

Diabetes: a global epidemic

Diabetes affects people in countries all over the world and its incidence is rapidly increasing. Indeed, diabetes is approaching epidemic proportions globally and it is estimated that by 2040 there will be 642 million people with diabetes1.

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Currently, there are 422 million adults worldwide who have diabetes, which equates to around one in every eleven people1,2. The World Health Organization estimates that diabetes causes 1.5 million deaths each year2 and thus diabetes is a major health concern across the globe.

Blood glucose levels

Diabetes is a chronic disease characterized by dangerously high levels of glucose in the blood. Usually, when more carbohydrates are ingested than are needed to satisfy the body's energy requirements, high blood glucose levels stimulate the production of insulin. The insulin then promotes the removal of excess glucose from the blood by converting it into glycogen that is stored in the liver. A normal blood glucose level is thus restored.

In diabetes, this glucose management system does not work effectively. This is either a consequence of not enough insulin being produced or the body not being able to effectively use the insulin it produces. Levels of glucose in the blood can consequently become dangerously high (hyperglycemia) and lead to a range of life-threatening conditions.

The most common form of the disease, accounting for 90%–95% of cases, is type 2 or non-insulin-dependent diabetes mellitus in which the production of insulin steadily declines. Its development is strongly associated with overeating, and type 2 diabetes was historically considered to be a late-onset disease. However, with the increasing prevalence of childhood obesity it is now being reported in children too.

Patients who are not able to produce any insulin are said to have type 1 diabetes, which usually presents in childhood.

The treatment of diabetes

Patients with type 1 diabetes require regular insulin injections to maintain blood glucose levels within the normal range.

In contrast, type 2 diabetes can be managed initially by reducing carbohydrate intake and then by taking oral medications that promote the effects of insulin. Such medications help control blood sugar levels via a range of mechanisms, including suppression of glucose production in the liver, blocking glucose absorption in to the blood, and stimulation of insulin release from pancreatic cells.

Although effective, medications for type 2 diabetes can have unwanted side effects, most commonly gut disturbances. Natural remedies have consequently been widely used to lower blood glucose levels2.

Natural anti-hyperglycemic remedies

The anti-diabetic potential of numerous plants has been investigated in the search for effective, well tolerated treatments for lowering blood glucose levels in patients with diabetes. Indeed, over 400 plants have been reported to have a glucose-lowering effect and herbal remedies have been widely used to lower blood glucose levels3.

In some cases, the insulinomimetic and anti-diabetic activity of these remedies has exceeded that achieved with conventional anti-diabetic agents. The mechanisms of action of these remedies are similar to those of mainstream anti-diabetic drugs, i.e., restore insulin production, or inhibit the intestinal absorption of glucose.

Since the side effects of current pharmacological treatments for type 2 diabetes can be unbearable for some patients, there is still considerable research activity focused on identifying new anti-diabetic agents from natural plants. The plant compounds frequently reported to have an anti-diabetic effect include glycosides, alkaloids, flavonoids, and carotenoids.

Using this knowledge, a further 400 plant species with the potential for having anti-hyperglycemic efficacy have been identified. It is hoped that ultimately this continued research into plant-based glucose-lowering agents will lead to the development of an effective drug for types 2 diabetes that has a low risk of adverse effects.

Isolation of plant extract with glucose lowering properties

The latest plant shown to possesses significant glucose-lowering properties is Pericampylus glaucus4, a tropical climbing plant native to southern Asia. This plant is well-known locally as a cure for fever, headache and asthma. In Malaysia, it has also been used to treat high blood sugar and hypercholesterolemia5.

The anti-hyperglycemic effects of Pericampylus glaucus have now been scientifically assessed in mice4. Pericampylus glaucus extract administered to STZ-induced diabetic rats was shown to significantly reduce blood glucose levels compared with untreated diabetic mice.

The reductions in glucose levels achieved with Pericampylus glaucus extract were similar to those seen in diabetic mice who received the marketed glucose-lowering drug glibenclamide. Moreover, after 24 hours, the diabetic mice that had been administered the plant extract showed greater reductions in blood glucose levels than the mice who had received glibenclamide.

Spectral analysis of the Pericampylus glaucus extract, conducted using the Bruker Biospin Avance 400 MHz NMR spectrophotometer, subsequently revealed a single active component. Using the chemical shift spectra of the extract, the compound was identified as 2-[(trimethylsilyl)-oxy]-, methyl ester (cas) methyl o-trimethylsilyl-salicylate.

This demonstration of the blood-glucose lowering activity of extract from the Pericampylus glaucus plant in mice has provided justification for further investigations into the suitability of this plant for use in the management of diabetes in man.

References

  1. International Diabetes Association. Diabetes Facts and Figures. Available at http://www.idf.org/about-diabetes/facts-figures
  2. World Health Organization Diabetes Fact Sheet 2017. Available at http://www.who.int/diabetes/en/
  3. Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed 2012;2:320‑330.
  4. Kifayatullah M, Shahimi M, Kaleemullah, Muhammad SK. Anti-diabetic Activity of Compound “2-[(trimethylsilyl) oxy] - Methyl Ester (cas) Methyl-o-trim-ethyl-silylsalicylate” Isolated from Pericampylus glaucus (Lam) Merr in STZ-Induced Diabetic Rats. J Basic Clin Pharma 2017;8:68‑73.
  5. Ong H, Chua S, Milow P. Ethno-medicinal plants used by the Temuan villagers in Kampung Jeram Kedah, Negeri Sembilan, Malaysia. Ethno Med. 2011;5:95-100.

About Bruker

Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI). Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI ,EPR and Time-Domain (TD) NMR. In addition.

Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research. Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.


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Last updated: May 19, 2017 at 1:02 PM

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