Effects of low molecular weight galactomannans based standardized fenugreek seed extract in subjects with high fat mass: A randomized, double-blind, placebo-controlled clinical study

The present investigation evaluated the effects of low molecular weight galactomannans-based standardized fenugreekseeds extract (LMWGAL-TF) on human subjects with high-fat mass for 8-weeks using a prospective, randomized,double-blind, placebo-controlled design. Twenty-four subjects with percent body fat were randomized to ingest acapsule of LMWGAL-TF (500 mg, once a day) or the matching placebo at a 1:1 ratio for 8 weeks. The outcomemeasurements were recorded at baseline, week-4, and week-8 (end of the treatment). The efficacy outcome includedfat mass (absolute, non-fat mass and %) by skinfold thickness method (along with triceps, suprailiac, and abdominal)and bioelectrical impedance analysis method, body weight, body mass index, and abdominal girth. The standardsafety parameters were measured, such as adverse events, vital signs, hematology, and biochemistry. Eight weeksof LMWGAL-TF supplementation showed significant reduction in suprailiac skinfold thickness (v/s baseline) andabdominal skinfold thickness (v/s baseline and v/s placebo), and percent fat mass, (v/s baseline). The LMWGAL-TFsupplementation was found to be safe and well-tolerated. In conclusion, LMWGAL-TF supplementation showedsafety and efficacy in reducing skinfold thickness (abdominal and suprailiac) and percent body fat in subjects with ahigh fat mass

Add-on therapy of herbal formulation rich in standardized fenugreek seed extract in type 2 diabetes mellitus patients with insulin therapy: An efficacy and safety study

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract (IND-2) add-on therapy in type 2 diabetes mellitus (T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial. Methods: T2DM patients (n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar (FBS) level between 100-140 mg/dL received IND-2 capsules (700 mg, thrice a day) for 16 weeks. The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16. Secondary end-points include post-prandial blood sugar level, glycosylated Hb (HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks. Safety and adverse events (AEs) were also assessed during the study. Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after add-on therapy of IND-2. However, add-on therapy of IND-2 significantly reduced (P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline. Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoprotein-cholesterol levels were significantly increased (P<0.01) after IND-2 add-on therapy. Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16. Additionally, add-on therapy of IND-2 did not produce any serious adverse events. Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia. Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.

Preclinical safety assessment of glycosides based standardized fenugreek seeds extract: Acute, subchronic toxicity and mutagenicity studies.

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.

Prophylactic efficacy and possible mechanisms of oligosaccharides based standardized fenugreek seed extract on high-fat diet-induced insulin resistance in C57BL/6 mice.

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.

Antidepressant effects of standardized extract of Commiphora mukul Engl. in olfactory bulbectomized rats

The objective of this work was to evaluate the effects of standardized hydroalcholic extract of Commiphora mukul (HECM) in animal model of chronic stress medicated depression, namely olfactory bulbectomy (OBX) model in rats. Effects of 14-day (subacute) oral pretreatment of HECM (50, 100 and 200 mg/kg) were evaluated on depression and stress related parameters on OBX rats. Separate groups for sham control, OBX control and positive controls namely imipramine (20 mg/kg), fluoxetine (30 mg/kg) and desipramine (15 mg/kg) were also maintained. Behavioral and physiological parameters in open field and elevated plus maze were recorded. HECM showed dose-dependent reversal of OBX-induced physiological effects such as reduction of body weight, body temperature, heart rate and serum sodium concentration. HECM also showed reversal effects on OBX induced food intake increase and hyperactivity in open field and elevated plus maze paradigm. In conclusion, HECM demonstrated restorative effects in OBX induced depression model in rats probably due to stress reliving mechanisms.

Modulatory activity of a polyphenolic fraction of Cinnamomum zeylanicum L. bark on multiple arms of immunity in normal and immunocompromised mice.

To evaluate immunomodulatory activity of polyphenolic fraction of Cinnamomum zeylanicumbark (PP-CZ) against infection-related conditions using normal and immune-compromised mice. The normal and cyclophosphamide (CYP)-induced immune-compromised mice were sensitized with SRBCs and PP-CZ (10, 25, and 50 mg/kg, p.o.) was administered orally for 7 days. The haemagglutinin (HA) antibody titres (primary and secondary) and delayed type hypersensitivity (DTH) response was measured at 7- and 14-days postimmunization, respectively. In separate experiments, effects of PP-CZ on numbers of resident peritoneal macrophages in peripheral blood mononuclear cell (PBMC), against host resistance (E coli-induced abdominal sepsis) and phagocytic activity against Candida albicans were evaluated in mice. PP-CZ had shown a have beneficial effects on multiple arms of theimmune system in animal models and improves humoral (antibody production), cellular (DTH) and innate (PMN phagocytosis) responses of the immune system, as well as numbers of resident peritoneal macrophages. PP-CZ also showed protection to mice against lethal E. coli abdominal sepsis. PP-CZ demonstrated significant immunomodulatory activity through multiple arms of immunity in normal and infection-related immuno-compromised conditions.

Therapeutic effects of standardized fenugreek seed extract on experimental urolithiasis in rats.

The objective of the present study was to investigate therapeutic efficacy of standardized fenugreek seed extract with trigonelline as marker (SFSE-T) in experimental urolithiasis in rats. Effects of subacute oral treatments of SFSE-T (30 and 60 mg/kg) and reference anti-urolithiasis drug, Cystone (750 mg/kg) were evaluated against 0.75% ethylene glycol (EG) and 1 % w/v ammonium chloride (AC) induced urolithiasis in rats. The biochemical (urinary and serum) and histopathological parameters were investigated. Subacute oral treatment of SFSE-T (60 mg/kg) showed reversal of EG+AC induced changes in urine (decreased 24-h urine output, pH, excretion of creatinine, citrate, and chloride and increased uric acid and oxalate excretion) and serum (increased creatine, uric acid and blood urea nitrogen) parameters and decreased creatine clearance. Histopathology examination of the kidneys sections from SFSE-T (60 mg/kg) treated rats showed lowered number of crystals, cell damage and tubulointerstitial damage index as compared with EG+AC control rats. Standardized fenugreek seed extracts showed promising therapeutic effect against experimental urolithiasis in rats.

Anorexic effect of (R)-sibutramine: comparison with (RS)-sibutramine [corrected] and (S)-sibutramine.

Sibutramine is one of the very few drugs that are approved for long-term treatment of obesity. Sibutramine is a racemic mixture (RS) containing two equal forms of the R(+) and S(-) enantiomers. In this paper, we have investigated comparative anorexic effect of sibutramine enantiomers and their recemate form in rats. After obtaining two days of baseline results, rats were administered orally either with (RS)-sibutramine or its enantiomers (R)- or (S)-sibutramine at dose levels of 5, 10, 20 mg/kg each for 4 days and body weight, food intake and water intake were measured daily. Locomotor activity score of each rat was also recorded on each day. R-Sibutramine and (RS)-sibutramine produced dose dependant decrease in the body weight and food intake. On the other hand, (S)-sibutramine was shown to increase in these parameters. Neither sibutramine nor it's enantiomers showed any consistent effects on spontaneous motor activity (SMA) scores. In conclusion, (R)-sibutramine is better anorexic than or (RS)-sibutramine or it's (S)-enantiomers.