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

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.

Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice.

The pharmacokinetics and tissue distribution of Gentiopicroside (GPS), one of the major active components of the Gentiana species of medicinal plants, was studied following oral and intravenous administration in mice. The distribution of GPS in mice after oral and intravenous doses could be fitted to a two-compartments open model. The serum half-life of GPS was 6.1 h and 2.8 h for intravenous and oral administration, respectively. The Tmax of GPS after oral administration was 0.50 h, and the bioavailability was 39.6%. The AUC gradient in individual tissues following intravenous administration was kidney >serum >liver >spleen >lung >thymus >fat >heart >muscle >stomach >intestinal >brain. The MRT gradient was muscle >serum >lung >spleen >lung >intestinal>heart >stomach >brain >liver >thymus >kidney >fat. Overall the data show that GPS could be absorbed rapidly in mice, but with a low bioavailability, and could distribute to tissues extensively, but was generally cleared quickly with short MRTs. The study demonstrates the need for repeated dosage, or better, a slow release formulation as an ideal means of administering GPS.