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We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

Fenugreek seeds (Trigonella foenum graecum L.) are assumed to have restorative and nutritive properties. The present work was designed to investigate the effects of a fenugreek seed extract on feeding behaviour. Experiments were performed to determine food consumption and motivation to eat as well as metabolic-endocrine changes in chronically treated animals. Male Wistar rats were given the seed extract orally (10 and 100 mg/day per 300 g body weight), mixed together with food, and control animals were monitored in parallel. The results show that chronic oral administration of the fenugreek extract significantly increases food intake and the motivation to eat. The treatment, however, does not prevent the anorexia nor the decreased motivation to eat induced by d-fenfluramine (2 mg/kg, IP). An increase in plasma insulin and a decrease in total cholesterol and very low-density lipoprotein (VLDL)-low-density lipoprotein (LDL) total cholesterol were also observed. In conclusion, chronic administration of a fenugreek seed extract enhances food consumption and motivation to eat in rats and also induces hyperinsulinemia as well as hypocholesterolemia.

The transformation of fenugreek subfractions, rich in steroid saponins, was studied upon their passage through the digestive tract to determine the contribution of saponins and/or diosgenin and other steroid sapogenins to the hypocholesterolemic effect of fenugreek seeds. Feces of alloxan diabetic dogs fed fenugreek subfractions were analyzed, and diosgenin, smilagenin and gitogenin were identified and measured using capillary gas chromatography/mass spectrometry. Our results show that saponins are, in part (about 57%), hydrolyzed into sapogenins in the digestive tract. It appears that saponins may be implicated, alone or together with diosgenin, in the observed hypocholesterolemic effect of fenugreek seeds in diabetic dogs.

The components of fenugreek seeds were separated and analyzed to determine which fraction of the seed had hypoglycemic activity. These fractions were administered orally to normal or diabetic dogs for 8 days. The effect on blood glucose and pancreatic hormones was studied in normal dogs. The lipid extract had no effect; the defatted fraction (50.2% fibers: gum 17.7%, hemicellulose 22%, cellulose 8.3%, lignin 2.2%) lowered basal blood glucose level, plasma glucagon and somatostatin levels and reduced the orally induced hyperglycemia. The addition of this fraction to the insulin treatment resulted in a decrease of hyperglycemia and glycosuria in diabetic dogs. The results indicate that the defatted part is responsible for the antidiabetic action. However, the present study does not permit one to know whether the effects are caused by an unknown pharmacological compound or by the gastrointestinal action of fibers.

The volatile components in chloroform extracts and essential oils from the seeds of Nigella damascena and Nigella sativa were analyzed by GC and GC/MS. The volatile compositions differed in the two species: N. damascena contained sesquiterpenes, including a large proportion of β-elemene (27.7% extract, 54.7% oil) and methyl 3-methoxy-N-methyl anthranilate (30.7% extract, 12.7% oil), which account for the characteristic aroma of this species, whereas only monoterpenes, including p-cymene (49.0% extract, 47.4% oil) and thymoquinone (20.6% extract, 20.8% oil), were detected in N. sativa. [ABSTRACT FROM AUTHOR]