ABSTRACT
Objective: To evaluate acute oral toxicity (AOT), subchronic toxicity, and mutagenic potential of glycosides based standardized fenugreek (Trigonella foenum graecum L.) seeds extract (SFSE-G). Materials and Methods: The AOT, subchronic (90-day repeated dose) toxicity and mutagenicity (reverse mutation test) of oral administration of SFSE-G were evaluated using Sprague-Dawley (SD) rats as per OECD guideline no. 423, No. 408 and 471 respectively. Results: The SFSE-G did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-days repeated dose of 250, 500 and 1000 mg/kgwith 28 days of recovery period) administration. The SFSE-G showed oral median lethal dose (LD50) more than 2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of SFSE-G was 1000 mg/kg in male rats and 500 mg/kg in female rats during subchronic toxicity study. Furthermore, SFSE-G did not show mutagenic potential in vitro. Conclusions: SFSE-G was found safe for acute and subchronic (90 days repeated dose) administration in rats with no mutagenic potential.
ABSTRACT
The present work was aimed to study the efficacy and possible mechanism of oligosaccharides based standardized fenugreek seed extract (SFSE-OS) on high-fat diet (HFD)-induced insulin resistance in male C57BL/6 mice. The effects of 12 weeks of oral administration of SFSE-OS (30, 60 and 100 mg/kg, twice daily) were evaluated on HFD fed mice for anthropomorphic, glycemic, gene expression related and histopathological parameters. Separate groups of mice with vehicle co-administered with HFD and low-fat diet (LFD) were maintained as HFD control and LFD control respectively. Twelve weeks of SFSE-OS (60 and 100 mg/kg, p.o.) administration showed significant prophylactic effects on HFD induced insulin resistance in terms of body weight, plasma glucose and insulin levels, glycated hemoglobin, insulin resistance (IR), area under the curve (AUC) of plasma glucose during oral glucose tolerance and intraperitoneal insulin tolerance. Furthermore, HFDinduced mRNA expression changes in adipose tissue, liver and skeletal muscle were prevented by SFSE-OS coadministration. Histology of sections of the pancreas showed the normal architecture in all groups of mice. SFSE-OS showed promising efficacy in prevention of HFD-induced insulin resistance through modulation of Glut-2, Glut-4, IRS-2 and SREBP-1c expression.
ABSTRACT
Background & objectives: Plant polyphenols have been known to exert anti-diabetic action and promote insulin action. The present study was carried out to compare the effects of administration of fenugreek seed polyphenolic extract (FPEt), quercetin and metformin (a positive control) in an acquired model of insulin resistance (IR). Methods: Adult male Wistar rats divided into seven groups (n=12). IR was induced in groups (groups 2, 3, 4 and 5) by feeding a high fructose diet (FRU) (60 g/100 g diet) for 60 days. From day 16, FRU rats were administered either FPEt (200 mg/kg bw) (group 3), quercetin (50mg/kg bw) (group 4) or metformin (50 mg/kg bw) (group 5) for the next 45 days. Group 1 served as normal control while groups 6 and 7 served as FPEt and quercetin controls respectively. Oral glucose tolerance test (OGTT) was done on day 59 to assess glucose tolerance. At the end of 60 days, the levels of glucose, insulin, triglycerides (TG) and free fatty acids (FFA) were measured in the blood and the activities of insulin-inducible and suppressible enzymes in cytosolic and mitochondrial fractions of liver and skeletal muscle. The extent of tyrosine phosphorylation of proteins in response to insulin was determined by assaying protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in liver. Results: Fructose caused increased levels of glucose, insulin, TG and FFA, alterations in insulin sensitivity indices, enzyme activities and reduced glycogen content. Higher PTP activity and lower PTK activity suggest reduced tyrosine phosphorylation status. Administration of FPEt or quercetin improved insulin sensitivity and tyrosine phosphorylation in fructose-fed animals and the effect was comparable with that of metformin. Interpretation & conclusions: Our findings indicated that FPEt and quercetin improved insulin signaling and sensitivity and thereby promoted the cellular actions of insulin in this model.