Mechanism of Antidiabetic Action of Compound GII Purified from Fenugreek (Trigonella foenum graecum) Seeds

Abstract

To study the mechanism of action of water soluble compound GII purified from fenugreek (Trigonella foenum graecum) seeds which was shown earlier to have antidiabetic effect in the subdiabetic, moderately and severely diabetic rabbits. In rabbits (1-1.5 kg bw) diabetes was induced by intravenous injection of 80 mg/kg bw of alloxan. They were fed with GII at a dose of 50 mg/kg bw daily once in the morning for 15 days in the subdiabetic and moderately diabetic and 30 days in the severely diabetic rabbits. Serum total cholesterol (TC), triglycerides (TG), LDL ? VLDL cholesterol [(LDL ? VLDL)C], HDL cholesterol [(HDL)C], total tissue lipids, glycogen and enzymes of carbohydrate metabolism (glycolysis, gluconeogenesis, polyol pathway) hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, aldose reductase and sorbitol dehydrogenase and antioxidant enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase were estimated. Liver and kidney function parameters were also estimated. Treatment with GII for 15 days in the subdiabetic and moderately diabetic rabbits and for 30 days in the severely diabetic rabbits (i) decreased the elevated lipids TC, TG, (LDL ? VLDL)C and increased the decreased (HDL)C, (ii) decreased the elevated liver and heart total lipids, TC and TG, (iii) increased the decreased liver and muscle glycogen, (iv) increased the decreased hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione peroxidase, (v) decreased the increased glucose-6-phosphatase, sorbitol dehydrogenase, aldose reductase. Results thus show that treatment with GII compound purified from fenugreek seeds for 15 days in the subdiabetic and moderately diabetic and 30 days in the severely diabetic rabbits corrects the altered serum lipids, tissue lipids, glycogen, enzymes of glycolysis, gluconeogenesis, glycogen metabolism, polyol pathway and antioxidant enzymes. Histopathological abnormalities (fatty infiltration and other cellular changes) seen in the pancreas, liver, heart and kidneys were repaired after treatment with GII. In fact partially damaged pancreas was repaired. Liver and kidney function test results were normal in the GII treated animals indicating that GII treatment is safe and free from any side effects.

Inhibition of Key Digestive Enzymes-Related to Diabetes and Hyperlipidemia and Protection of Liver-Kidney Functions by Trigonelline in Diabetic Rats

“…The protection of pancreas architecture led to an increase in insulin rate, and consequently, the regulation of glucose metabolism and an increase in body, hepatic, and renal weights (Table 1). These results, in agreement with findings recently reported by Puri et al [6]), have reported that the administration of fenugreek trigonelline to diabetic rats modulates key enzymes of metabolism such as hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, sorbitol dehydrogenase, and aldose reductase, and also the glucogen rate in muscle and the liver.…”

“…One of the therapeutic approaches proposed so far for the decrease of drug-treated diabetes is based on the retardation of glucose absorption through the inhibition of carbohydrate-hydrolyzing enzymes, i.e. ; α-amylase and maltase in the intestine [6]. …”

“…One of the therapeutic approaches used to decrease drug-treated diabetes and its complications is to retard the absorption of glucose and lipid through the inhibition of carbohydrate-hydrolyzing enzymes, i.e., α-amylase, maltase, and lipase in the intestine [3–5]. There are reports on the use of fenugreek seed extracts in diabetes mellitus [6, 7]. The seeds of this plant have been used as a traditional remedy for conditions including gastrointestinal disorders, gout, wound healing, inflammation, hyperlipidemia, and diabetes.…”

“…The seeds of this plant have been used as a traditional remedy for conditions including gastrointestinal disorders, gout, wound healing, inflammation, hyperlipidemia, and diabetes. The biological and pharmacological actions of fenugreek are attributed to the variety of its constituents, namely: steroids as diosgenin, alkaloids as trigonelline [6, 7], and amino acids as 4-Hydroxyisoleucine [8]. In fact, it is reported that the purification alkaloid (GII) from fenugreek and other compounds from fenugreek seeds were demonstrated to be useful in subdiabetic, moderately diabetic, and severely diabetic rabbits [9, 10].…”

Modulatory Effect of an Isolated Triglyceride from Fenugreek Seed Oil on of α-Amylase, Lipase and ACE Activities, Liver-Kidney Functions and Metabolic Disorders of Diabetic Rats

“…Acarbose also decreased the blood glucose concentrations at 30 and 60 min after starch loading. In fact, previous studies have reported that administration of FSO to diabetic rats is associated with regulation of enzymes of carbohydrate metabolism such as hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, aldose reductase and sorbitol dehydrogenase in liver of diabetic rats 35 .…”