Anand Swaroop

Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview

A large number of investigations have demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and degenerative diseases including cardiovascular dysfunctions, acute and chronic stress, gastrointestinal distress, neurological disorders, pancreatitis, various stages of neoplastic processes and carcinogenesis including detoxification of carcinogenic metabolites. GSP exhibited potent free radical scavenging abilities in both in vitro and in vivo models. GSP exerted significant in vivo protection against structurally diverse drug and chemical-induced hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity and spleentoxicity. GSP also protected against idarubicin and 4-hydroxyperoxy-cyclophosphamide-induced cytotoxicity toward human normal liver cells. GSP exhibited selective cytotoxicity toward selected human cancer cells, while enhancing the growth and viability of normal cells. GSP exhibited potent modulatory effects of pro-apoptotic and apoptotic regulatory bcl-XL, p53, c-myc, c-JUN, JNK-1 and CD36 genes. Long-term exposure to GSP may serve as a novel chemoprotectant against three stages of DMN-induced liver carcinogenesis and tumorigenesis including initiation, promotion and progression. GSP may selectively protect against oxidative stress, genomic integrity and cell death patterns in vivo. These results demonstrate that GSP may serve as a novel therapeutic intervention against carcinogenesis.

Safety, efficacy and toxicological evaluation of a novel, patented anti-diabetic extract of Trigonella Foenum-Graecum seed extract (Fenfuro)

Abstract Safety and anti-diabetic efficacy of a novel, proprietary Trigonella foenum-graecum seed extract [novel fenugreek extract (FE), Fenfuro™, CR0010810) enriched in furostanolic saponins (>60% w/w, HPLC) were assessed. Concerning safety, we undertook studies dealing with acute oral toxicity, 28-d sub-chronic toxicity and Ames’ bacterial reverse mutation assay that revealed no toxicity. Concerning efficacy, we examined beneficial effects of the extract on rats with type 2 diabetes (T2D). Male Sprague–Dawley rats received a high-fat diet for 2 weeks followed by streptozotocin (STZ, 35 mg/kg i.p.) to produce T2D. Seven days post-STZ, rats showing ≥300 mg/dl fasting plasma glucose level (PGL) were included in the study. FE (150- or 450- mg/kg p.o.) and glipizide (5 mg/kg p.o.) were administered once daily for 20 d and then twice daily for another 10 d (total 30 d). Blood samples were collected at 0, 10, 20 and 30 d of treatment and estimated for fasting plasma triglyceride (PTG), total cholesterol and insulin levels. After 30 d, FE and glipizide-treated diabetic animals were treated in combination with or without metformin (100 mg/kg) twice daily for another 10 d. FE did not influence body weight, feed and water intake. FE (150 mg/kg p.o.) reduced PTG levels in T2D rats by 22%, 24.6% and 29% at 10, 20 and 30 d of treatment, respectively, while glipizide (5 mg/kg p.o.) reduced the PTG levels by 57.4%, 46.2% and 39.4% at these time points. FE (450 mg/kg) treatment in STZ-induced diabetic rats produced significant hypoglycemic activity (approximately 31.5%) as compared to insulin (48.2% with 1 U/kg i.p.). FE (150 mg/kg p.o.) and metformin (100 mg/kg p.o.) combined produced significant reduction (20.7%) of PGL in T2D rats. No adverse effects were observed. We conclude after extensive in vitro and in vivo safety and efficacy studies that FE is safe and effective in treating T2D.

A small plant with big benefits: Fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion

Plant-derived natural products have long-standing utility toward treating degenerative diseases. It is estimated that about two-thirds of world population depend on traditional medicine for primary medical needs. Fenugreek (Trigonella foenum-graecum Linn.), a short-living annual medicinal plant belonging to Fabaceae family, is used extensively in various parts of the world as herb, food, spice, and traditional medicine. Fenugreek is considered as one of the oldest medicinal plants and its health-promoting effects have been cited in Ayurveda and traditional Chinese medicine. The investigations into the chemical composition and pharmacological actions have seen a renaissance in recent years. Extensive preclinical and clinical research have outlined the pharmaceutical uses of fenugreek as antidiabetic, antihyperlipidemic, antiobesity, anticancer, anti-inflammatory, antioxidant, antifungal, antibacterial, galactogogue and for miscellaneous pharmacological effects, including improving womens health. The pharmacological actions of fenugreek are attributed to diverse array of phytoconstituents. The phytochemical analysis reveals the presence of steroids, alkaloids, saponins, polyphenols, flavonoids, lipids, carbohydrates, amino acids, and hydrocarbons. This review aims to summarize and critically analyze the current available literature to understand the potential of fenugreek for disease prevention and health improvement with special emphasis on cellular and molecular mechanisms. Current challenges and new directions of research on fenugreek are also discussed.

A multicenter clinical study to determine the efficacy of a novel fenugreek seed (Trigonella foenum-graecum) extract (Fenfuro™) in patients with type 2 diabetes

Background Trigonella foenum-graecum (fenugreek) seeds are known to exhibit potent antioxidant, hypoglycemic, and nephroprotective activities, as well as serve as excellent membrane stabilizers especially because of their content of novel furostanolic saponins. Our previous studies exhibited the broad spectrum safety and efficacy of Fenfuro, a novel T. foenum-graecum seed extract enriched in furostanolic saponins, in type 2 diabetes (T2D) in rats. Design This multicenter, randomized, placebo-controlled, double-blind, add-on clinical study evaluated over a period of 90 consecutive days the efficacy of Fenfuro (daily dosage: 500 mg bid) in 154 subjects (male: 108; female: 46; age: 25–60 years) with T2D. Methods This study examined the body weight, blood pressure, and pulse rate, as well as the efficacy of Fenfuro on fasting and post-prandial plasma sugar (mg/dL), glycosylated hemoglobin (HbA1c), and fasting and post-prandial C-peptide levels. Results Fenfuro caused significant reduction in both fasting plasma and post-prandial blood sugar levels. Approximately 83% of the subjects reported decreases in fasting plasma sugar levels in the Fenfuro-treated group as compared to 62% in the placebo group, while 89% of the subjects demonstrated reduction in post-prandial plasma sugar levels in the Fenfuro-treated group as compared to 72% in the placebo group. HbA1c levels were reduced in both placebo and treatment groups. The decrease in HbA1c levels was significant in both groups as compared to respective baseline values. A significant increase in fasting and post-prandial C-peptide levels compared to the respective baseline values was observed, while no significant changes in fasting and post-prandial C-peptide levels were observed between the two groups. No significant adverse effects were observed by blood chemistry analyses. Furthermore, 48.8% of the subjects reported reduced dosage of anti-diabetic therapy in the Fenfuro-treated group, whereas 18.05% reported reduced dosage of anti-diabetic therapy in the placebo group. Conclusion In summary, Fenfuro proved safe and efficacious in ameliorating the symptoms of T2D in humans.

Furostanolic saponins from Trigonella foenum-graecum alleviate diet-induced glucose intolerance and hepatic fat accumulation.

SCOPE The objective of this study was to evaluate the effect of fenugreek furostanolic saponins (Fenfuro(TM) ) either alone or in combination with chlorogenic acid (GCB-70(TM) ) on insulin resistance in mice. METHODS AND RESULTS Male C57BL/6J mice were subjected to a normal or high-fat diet (HFD) and were randomly assigned to receive Fenfuro(TM) , GCB-70(TM) , or their combination for 24 wk. Metabolic parameters, glucose tolerance, serum triglycerides, cardiac function, and hepatic insulin signaling were evaluated using indirect open-circuit calorimetry, intraperitoneal glucose tolerance test, oil red O staining, echocardiography, and Western blotting, respectively. Intraperitoneal glucose tolerance test revealed glucose intolerance in the mice receiving HFD, which was attenuated by Fenfuro(TM) . Serum triglyceride that was elevated following an HFD was reconciled by both Fenfuro(TM) and the combination. HFD compromised myocardial contractile function, which was unaffected by the treatment. Insulin-stimulated phosphorylation of Protein kinase B (AKT) in the liver was attenuated in mice receiving HFD, which was partially rescued by GCB-70(TM) . Neither treatment altered metabolic parameters or energy expenditure. CONCLUSION Collectively, our data suggest that fenugreek furostanolic saponins and green coffee bean extract may have potential benefits in treating insulin resistance and related conditions.

Efficacy of a Novel Fenugreek Seed Extract (Trigonella foenum-graecum, FurocystTM) in Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders among women of reproductive age causing irregular menstrual cycles, excessive body or facial hair, miscarriage and infertility. The latter being a most common PCOS symptoms. Because the symptoms are seemingly unrelated to one another, PCOS is often overlooked and undiagnosed. The present study is an open label, one-arm, non-randomized, post-marketing surveillance study in 50 premenopausal women (18-45 years, BMI<42) diagnosed with PCOS using a novel Trigonella foenum-graecum seed extract (fenugreek seed extract, Furocyst, 2 capsules of 500 mg each/day) extract, enriched in approximately 40% furostanolic saponins, over a period of 90 consecutive days. The study was conducted to determine its efficacy on the reduction of ovarian volume and the number of ovarian cysts. Ethical committee approval was obtained for this study. Furocyst treatment caused significant reduction in ovary volume. Approximately 46% of study population showed reduction in cyst size, while 36% of subjects showed complete dissolution of cyst. It is important to mention that 71% of subjects reported the return of regular menstrual cycle on completion of the treatment and 12% of subjects subsequently became pregnant. Overall, 94% of patients benefitted from the regimen. Significant increases in luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were observed compared to the baseline values. Extensive blood chemistry, hematological and biochemical assays demonstrated the broad-spectrum safety. Furocyst caused significant decrease in both ovarian volume and the number of ovarian cysts. Serum ALT, BUN and CK were assessed to demonstrate the broad-spectrum safety of Furocyst. No significant adverse effects were observed. In summary, Furocyst was efficacious in ameliorating the symptoms of PCOS.

General Lack of Correlations between Age and Signs of the Metabolic Syndrome in Subjects with Non-diabetic Fasting Glucose Values

ABSTRACT Background: Insulin resistance and advancing age are well-recognized risk factors for metabolic syndrome. Recent reports indicate that fasting glucose levels in non-diabetic patients correlate appropriately with the development of certain elements in metabolic syndrome, which suggest a cause–effect relationship with insulin resistance. Objective: The present investigation assessed whether a significant association exists between chronological age and various elements of metabolic syndrome in this same group of subjects possessing non-diabetic fasting glucose levels. Methods: Baseline data were taken from 288 subjects (age 17–87 years) with fasting glucose levels ≤ 125 mg/dl. Correlations between chronological age and different metabolic parameters were assessed to determine any statistically significant relationships and compare these with previously demonstrated metabolic parameters. Results: With the exception of systolic blood pressure, the following correlations between age and components of metabolic syndrome were not significant or even significant in the opposite direction compared to those found in the same population using fasting glucose as the independent variable: body weight, body fat, diastolic blood pressure, white blood cell count (WBC)/neutrophil count, and circulating levels of insulin, high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Although systolic blood pressure still increased, it was to a lesser extent than might be expected. Conclusions: In the present investigation, a cross-sectional analysis was carried out over a wide age range of subjects. It is noteworthy that fasting glucose levels and the other major elements of metabolic syndrome did not change significantly with advancing age. These results demonstrate that decreasing insulin resistance and fasting glucose levels may be an important way to overcome the adverse effects and perturbations of advancing age-induced consequences of metabolic syndrome.

Efficacy of FurosapTM, a novel Trigonella foenum-graecum seed extract, in Enhancing Testosterone Level and Improving Sperm Profile in Male Volunteers

Background: Dietary fiber rich fenugreek (Trigonella foenum-graecum) seeds have exhibited cardioprotective, hypolipidemic and other health benefits. Furosap (FS), an innovative, patented, 20% protodioscin-enriched extract was developed in our laboratory from fenugreek seeds. This study examined the free and total testosterone levels, sperm profile and morphology, sexual health, mood and mental alertness, and broad spectrum safety parameters of FS in 50 male volunteers following supplementation over a period of 12 weeks. Methods: Institutional Review Board (IRB) and other regulatory approvals were obtained for our study. This one-arm, open-labelled, multi-center study was conducted in 50 male volunteers (age: 35 to 65 years) over a period of 12 weeks to determine the efficacy of FS (500 mg/day/subject) on free and total testosterone levels, sperm profile, sperm morphology, libido and sexual health, mood and mental alertness, and broad spectrum safety parameters. Results: Free testosterone levels were improved up to 46% in 90% of the study population. 85.4% of the study population showed improvements in sperm counts. Sperm morphology improved in 14.6% of volunteers. Majority of the subjects enrolled in the study demonstrated improvements in mental alertness and mood. Furthermore, cardiovascular health and libido were significantly improved. Extensive safety parameters were evaluated which included blood chemistry data. No significant changes were observed in serum lipid function, cholesterol, triglyceride, HDL and LDL levels, hemogram (CBC), hepatotoxicity and nephrotoxicity. Conclusion: Overall, the results demonstrate that FS, enriched in 20% protodioscin, is safe and effective in attenuating testosterone levels, healthy sperm profile, mental alertness, cardiovascular health and overall performance in human subjects.

Longitudinal Examination of Links Between Risk Factors for the Metabolic Syndrome and Both Age and Fasting Glucose Levels in Nondiabetic Subjects

ABSTRACT Background: Previous evaluations in nondiabetic subjects revealed statistically significant correlations between fasting blood glucose (FBG) levels used as an estimate of insulin resistance and many components constituting the metabolic syndrome. Similar significant correlations were not found employing chronological age as the independent variable in the same nondiabetic individuals. Objective: The major purpose here was to replicate as well as corroborate the previous cross-sectional observations, emphasizing results obtained from data collected longitudinally. Methods: Material was assessed from 99 nondiabetic volunteers who had undergone 2 separate baseline measurements carried out over a minimum of 5 and up to a maximum of 20 years. Results: Findings from the starting baseline measurements mimicked many observations perceived in the earlier published cross-sectional material. The following correlations with elements constituting the metabolic syndrome using FBG as an independent variable were once more statistically significantly positive: scale weight, fat mass, circulating levels of triglycerides and high-sensitivity C-reactive protein (hsCRP). High-density lipoprotein (HDL) cholesterol was once again appropriately significant in a negative direction. In contrast, the same correlations were generally nonsignificant when age replaced FBG as the independent variable. Examining the 2 data sets over the 5–20-year intervals, FBG increased statistically significantly over time. However, the average increase clinically was relatively minor: −92.1 mg/dL ± 1.1 (SEM) vs 95.1 mg/dL ± 1.1 (SEM), p < 0.007. When the actual changes (delta) in the dependent parameters were correlated with the individual passages of time (intervals in years), only downward changes in aspartate aminotransferase (AST) levels were statistically significant. Fat-free mass showed a trend downward, whereas fat mass, trunk fat, and triglycerides merely demonstrated trends upward. Conclusion: Current findings gathered over years are consistent with the original hypothesis that maintaining relatively low, stable circulating glucose levels during aging retards the development and intensity of many common manifestations of the metabolic syndrome.

Blood Pressure Regulation: Reviewing Evidence for Interplay Between Common Dietary Sugars and Table Salt

ABSTRACT A popular concept is that the significant global progression in prevalence and intensification of elevated blood pressure (BP) levels is due in part to dietary indiscretions. Excess intake of several food sources causing overweight/obesity plays an important role in BP perturbations. However, certain nutrients are involved in ways other than via body fat accumulation, particularly table salt (sodium chloride) and popular refined carbohydrates like dietary sugars (sucrose, fructose, high fructose corn syrup). In nondiabetics and diabetics, several functions of salt and sugar influence BP and metabolism. For example, salt intake is linked to volume expansion, insulin resistance, and hypertension, while sugar intake is associated with enhanced salt sensitivity via urinary sodium retention, insulin resistance, and hypertension. The key postulate evaluated here is that when two popular nutrients—salt and dietary sugars—are consumed together in adequate amounts, their respective individual BP effects are significantly amplified. In previous laboratory studies, a sugar challenge did not increase BP in the face of marked sodium depletion, and combining sugar and salt challenges caused a synergistic BP elevation. Among examples of amplification on the clinical side, the greatest increases in BP following sugar challenges were seen in diabetic subjects having the highest sodium excretion. Interplay between table salt and common dietary sugars in BP regulation is a reasonable postulate and should be carefully considered when developing optimal prevention and treatment regimens to ameliorate the worldwide crisis arising from harmful elevated BP levels.