Non-insulin dependent anti-diabetic activity of (2S, 3R, 4S) 4-hydroxyisoleucine of fenugreek (Trigonella foenum graecum) in streptozotocin-induced type I diabetic rats

Phytomedicine. 2012 May 15;19(7):571-4. doi: 10.1016/j.phymed.2012.01.004. Epub 2012 Mar 6.


The seeds of fenugreek, Trigonella foenum graecum, commonly used as a spice in Middle Eastern countries and widely used in south Asia and Europe, are known to have anti-diabetic properties. They contain an unusual amino acid (2S, 3R, 4S) 4-hydroxyisoleucine (4HO-Ile), so far found only in fenugreek, which has anti-diabetic properties of enhancing insulin secretion under hyperglycaemic conditions, and increasing insulin sensitivity. Here we describe for the first time the anti-diabetic activity of 4HO-Ile in a model of type I diabetes, streptozotocin-treated rats, where levels of insulin are much reduced, by 65%, compared to normal animals. Treatment of diabetic rats with daily doses of 4HO-Ile at 50 mg/kg/day for four weeks could reduce plasma glucose in the diabetic group. Moreover the high levels of lipids (cholesterol, HDL, LDL and triglycerides) and uric acid in the diabetic rats, could be restored to levels found in non-diabetic controls by the treatment with 4HO-Ile. These results demonstrate that 4HO-Ile has significant anti-diabetic activities that are independent of insulin and suggest the potential of 4HO-Ile as an adjunct to diabetes treatment and for type 1 as well as type 2 diabetes.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood*
  • Isoleucine / analogs & derivatives*
  • Isoleucine / pharmacology
  • Isoleucine / therapeutic use
  • Lipids / blood
  • Male
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Wistar
  • Seeds
  • Trigonella / chemistry*
  • Uric Acid / blood


  • 4-hydroxyisoleucine
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Plant Extracts
  • Isoleucine
  • Uric Acid