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The fenugreek plant (Trigonella foenum-graecum) is traditionally known for its anti-diabetic properties owing to its high content of furostanolic saponins, which can synergistically treat many human ailments. Non-enzymatic protein glycation leading to the formation of Advanced Glycation End products (AGE) is a common pathophysiology observed in diabetic or prediabetic individuals, which can initiate the development of neurodegenerative disorders. A potent cellular source of glycation is Methyl Glyoxal, a highly reactive dicarbonyl formed as a glycolytic byproduct. We demonstrate the in vitro glycation arresting potential of Fenfuro®, a novel patented formulation of Fenugreek seed extract with clinically proven anti-diabetic properties, in Methyl-Glyoxal (MGO) adducts of three abundant amyloidogenic cellular proteins, alpha-synuclein, Serum albumin, and Lysozyme. A 0.25% w/v Fenfuro® was able to effectively arrest glycation by more than 50% in all three proteins, as evidenced by AGE fluorescence. Glycation-induced amyloid formation was also arrested by more than 36%, 14% and 15% for BSA, Alpha-synuclein and Lysozyme respectively. An increase in MW by attachment of MGO was also partially prevented by Fenfuro® as confirmed by SDS-PAGE analysis. Glycation resulted in enhanced aggregation of the three proteins as revealed by Native PAGE and Dynamic Light Scattering. However, in the presence of Fenfuro®, aggregation was arrested substantially, and the normal size distribution was restored. The results cumulatively indicated the lesser explored potential of direct inhibition of glycation by fenugreek seed in addition to its proven role in alleviating insulin resistance. Fenfuro® boosts its therapeutic potential as an effective phytotherapeutic to arrest Type 2 diabetes.
Fenfuro® is a novel patented formulation of Fenugreek seed extract with more than 45% furostanolic saponins and anti-diabetic property free from any side effect as established through clinical study.In the present study, the role of Fenfuro® in arresting in vitro AGE formation and glycation-induced amyloid formation has been demonstrated with the help of three amyloidogenic proteins, namely Human Lysozyme, Human alpha-synuclein and Bovine Serum Albumin using Methyl Glyoxal as the glycating agent.A 0.25% (w/v) ethanolic solution of Fenfuro® resulted in more than 50% arrest in glycation with simultaneous prevention of aggregation as demonstrated by native PAGE, DLS and inhibition of development of Thio-T positive amyloid like entities.The studies collectively aim toward the development of a safe therapeutic method for arresting protein glycation through direct physical intervention.
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Withania somnifera (L.) Dunal, popularly known as Ashwagandha or Indian ginseng, is well acclaimed for its health-enhancing effects, including its potent immunomodulatory, anti-inflammatory, neuroprotective, and anti-tumorigenic properties. The prime biological effectors of these attributes are a diverse group of ergostane-based steroidal lactones termed withanolides. Withanones and withanosides are distributed differentially across the plant body, whereas withanolides and withanones are known to be more abundant in leaves, while withanosides are found exclusively in the roots of the plants. Standardized W. somnifera extract is Generally Recognized as Safe (GRAS)-affirmed, however, moderate to severe toxic manifestations may occur at high dosages. Withaferin A, which also happens to be the primary bioactive ingredient for the effectiveness of this plant. There have been contrasting reports regarding the distribution of withaferin A in W. somnifera. While most reports state that the roots of the plant have the highest concentrations of this phytochemical, several others have indicated that leaves can accumulate withaferin A in proportionately higher amounts. A comprehensive survey of the available reports suggests that the biological effects of Ashwagandha are grossly synergistic in nature, with many withanolides together mediating the desired physiological effect. In addition, an assorted formulation of withanolides can also neutralize the toxic effects (if any) associated with withaferin A. This mini-review presents a fresh take on the recent developments regarding the safety and toxicity of the plant, along with a critical assessment of the use of roots against leaves as well as whole plants to develop therapeutic formulations. Going by the currently available scientific evidence, it is safe to infer that the use of whole plant formulations instead of exclusively root or leaf recipes may present the best possible option for further exploration of therapeutic benefits from this novel medicinal plant.HighlightsTherapeutic potential of withanolides owes to the presence of α,ß unsaturated ketone which binds to amines, alcohols, and esters and 5ß, 6ß epoxy group which react with side chain thiols of proteins.At concentrations above NOAEL (no observed adverse effect level), the same mechanisms contribute towards toxicity of the molecule.Although withanosides are found exclusively in roots, whole plants have higher contents of withanones and withanolides.Whole plant-based formulations have other metabolites which can nullify the toxicity associated with roots.Extracts made from whole plants, therefore can holistically impart all therapeutic benefits as well as mitigate toxicity.
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Withania , Witanólidos , Witanólidos/toxicidad , Witanólidos/química , Witanólidos/metabolismo , Withania/química , Withania/metabolismo , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Hojas de la Planta/química , Raíces de Plantas/química , Raíces de Plantas/metabolismoRESUMEN
Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid ß. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.
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Antioxidantes , Cofactor PQQ , Péptidos beta-Amiloides , Animales , Peso Corporal , Femenino , Hormonas , Masculino , Factor de Crecimiento Nervioso , Cofactor PQQ/toxicidad , Conejos , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Receptores de Factor de Crecimiento Nervioso , SemenRESUMEN
BACKGROUND: A gradual upward progression of blood pressure (BP) occurs regularly in most humans during aging. This is unfortunate, because it is generally recognized that elevation of BP, even when relatively mild, is eventually detrimental to human health. Accordingly, considerably more understanding of the pathophysiology behind such a phenomenon is important in order to institute the correct remedies. Two components of the ubiquitous metabolic syndrome (MS) with nutritional implications, elevated insulin resistance (IR) and excess body fat mass (FM), are often postulated to be critical driving forces behind the elevated BP that is common with aging. The current study, therefore, focuses on the presence and importance of IR and/or body FM in BP regulation of non-diabetics over the lifespan. METHODOLOGY: In cross sectional analyses, baseline data obtained from healthy, non-diabetic volunteers involved in prior clinical studies were analyzed by examining links between FBG measurements used as a surrogate for IR and body FM through their individual and combined effects on BP. RESULTS: A significant positive correlation was found between FBG and FM and also between each employed individually as independent variables to the dependent BP and heart rate (HR) variables. In volunteers with higher body FM compared to lower, average systolic BP (SBP) values are increased to some extent at the same FBG measurement suggesting that other factors related to FM in addition to IR are the basis for slight pressure differences. Considering quartiles based upon levels of FM and FBG, low FM-low FBG display significantly reduced average SBP, diastolic blood pressure (DBP), and HR compared to the upper FM-FBG quartiles. While readings of FBG and FM display a decline in elderly subjects after age 70 years (aging paradox), such does not occur with SBP. CONCLUSIONS: IR is a major driving force behind BP regulation even in non-diabetics. FM influences BP substantially through its relationship with IR and also via other mechanisms directly linked to FM.
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Resistencia a la Insulina , Tejido Adiposo , Anciano , Envejecimiento , Presión Sanguínea , Estudios Transversales , HumanosRESUMEN
OBJECTIVE: Many medical disorders comprising the metabolic syndrome (MS) are becoming increasingly prominent worldwide. Accordingly, much more knowledge is necessary to design the best preventive and therapeutic regimens to combat them effectively. This investigation examines the manner and magnitude of any interplay between body fat mass (FM) and insulin resistance (IR) in the evolution of these disorders using fasting blood glucose (FBG) as the latter's surrogate. Two components of MS, IR and body FM, appear to be particularly important because they have been postulated to be primary driving forces behind the other coexisting entities. Whether and how these two components interact is uncertain to some extent. METHOD: Baseline data obtained from healthy, non-diabetic volunteers involved in a number of prior clinical studies were analyzed by examining links between FBG and FM through their individual as well as combined effects on various components of MS. RESULTS: The present study consists of three phases. Phase 1 establishes that FM, similar to FBG, acting as an independent variable correlates significantly with various components of MS. The results even imply that FM offers a better measure for estimating generalized inflammation. Further, implied from findings in phase 2 is that FM influences inflammation not only by further augmenting IR but by additional means as well. In phase 3, where quartiles were developed based upon FBG and FM levels, the combination of relatively low FM/low FBG possesses significantly less proclivity for intensifying metabolic risk factors compared to the high FM/high FBG subset. CONCLUSIONS: Body FM through augmenting IR as well as another mechanism(s) markedly influences optimal fitness in seemingly normal healthy, non-diabetic volunteers. Maintaining the lowest reasonable levels of IR or body FM should bring one closer to long-term, ideal health, but improving the two jointly is an even better option.
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Resistencia a la Insulina , Síndrome Metabólico , Tejido Adiposo , Humanos , Factores de RiesgoRESUMEN
Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.Key teaching pointsVitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc.Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality.Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation.Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19.
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COVID-19 , Influenza Pandémica, 1918-1919 , Deficiencia de Vitamina D , Anciano , Humanos , SARS-CoV-2 , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlRESUMEN
Background: Significant inverse correlations between circulating vitamin D3 and the presence and strength of common clinical entities influenced by insulin resistance (IR) have been reported. Among these entities are common maladies such as the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Since hypovitaminosis D3 is considered a common worldwide health disturbance, the consequences emanating from such relationships once soundly established might reasonably be ameliorated by vitamin replacement. Accordingly, a need exists for definitive confirmatory support for the existence of these linkages particularly in ordinary, relatively healthy individuals.Methodology: Many aspects of MS and NAFLD were examined in healthy females via linear regression analyses to determine significant correlations mainly using vitamin D3 and fasting blood glucose (FBG), the latter a surrogate for IR, as independent variables.Results: A descending linear regression between vitamin D3 and FBG did not reach full statistical significance, but a negative correlation of vitamin D3 with HbA1C was statistically significant and that with circulating insulin concentrations showed a downward statistical trend. These findings are consistent with previous ones by others suggesting an ameliorating effect of vitamin D3 on IR. Body weight, body mass index (BMI), and body fat correlated statistically significantly with vitamin D3 levels, as did systolic blood pressure. Again, these correlations were negative instead of positive unlike the case when FBG was the independent variable. The significant negative correlation of ALT with vitamin D3 was also consistent with previous reports that higher circulating vitamin D3 favorably influences the extent and intensity of NAFLD.Conclusions: Employing FBG as a surrogate for IR and ALT for status of NAFLD, linear correlations reasonably suggest that increasing circulating vitamin D3 can favorably influence the initial development of and/or strength of risk factors for MS including NAFLD in relatively fit females.
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Resistencia a la Insulina , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Colecalciferol , Femenino , Voluntarios Sanos , HumanosRESUMEN
Objective: Obesity is growing at epidemic proportions worldwide. Natural compounds curcumin and α-lipoic acid have been shown to reduce body-weight gain in both preclinical and clinical studies. This study examined the effect of a combination of curcumin and α-lipoic acid on weight gain and adiposity in high-fat-diet (HFD)-fed mice. Methods: C57BL6 mice (7 weeks old) were randomly assigned to receive either HFD (60% fat) or a normal diet (ND, 10% fat) for a 12-week period, following which the mice receiving HFD were further assigned to supplemental curcumin (0.07%), α-lipoic acid (0.2%), or a combination of curcumin and α-lipoic acid formulated into the HFD for a further 12 weeks. Food intake and body mass were determined on a weekly basis. Body fat composition was determined by dual energy X-ray absorptiometry. Results: Treatment with both curcumin and α-lipoic acid significantly reduced body weight gain in HFD-treated mice, and the combination was more effective in attenuating body weight compared to the individual agents. Food intake and caloric intake were significantly lower in the mice that received α-lipoic acid. Percentage body fat and fat mass and lean body mass, which were increased following HFD feeding, were attenuated in the mice receiving curcumin and the combination. Lean mass was also elevated in the mice that were subjected to an HFD, which was unaltered by curcumin or the combination. Conclusions: Taken together, the combination of curcumin and α-lipoic acid exhibits an additive effect in reducing weight gain and adiposity in response to high-fat feeding.
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Adiposidad/efectos de los fármacos , Curcumina/farmacología , Dieta Alta en Grasa , Ácido Tióctico/farmacología , Aumento de Peso/efectos de los fármacos , Animales , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Background: Medical professionals attribute a crucial role in the development of several age-related, chronic health maladies to glucose-insulin perturbations - particularly, discernible insulin resistance (IR). However, little information is available concerning the degree to which relatively minor changes in IR participate over time in overall aging population, e.g., when circulating glucose and/or insulin concentrations are consistently within the higher end of normally accepted ranges. Objective: Obtaining precise knowledge is important, because proper nutritional management has the distinct capability of ameliorating the consequences. Methods: Five key concepts are suggested to underpin current thinking as to the applicable mechanisms and these are (1) the practical use of fasting blood glucose (FBG) levels as an estimate of IR, (2) the potential role of even slightly aberrant insulin regulation over time in the aging process, (3) the implementation of "continuum of risks" rather than checkpoints in considering prevention, (4) the presence and meaning of an aging paradox discovered in a recent study, and (5) the importance nutritional considerations in the "deadly triangle" as key factors in aging. Conclusions: Maintaining relatively low levels of FBG representing IR during aging via nutritional means has the potential to deliver a longer, more healthful lifespan as well as ameliorate many adverse manifestations of aging.
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Envejecimiento/sangre , Glucemia/metabolismo , Fenómenos Fisiológicos Nutricionales del Anciano/fisiología , Resistencia a la Insulina/fisiología , Insulina/sangre , Anciano , Anciano de 80 o más Años , Femenino , Humanos , MasculinoRESUMEN
Background: Two facts are generally recognized: (1) development of nonalcoholic fatty liver disease (NAFLD) is consistently linked to insulin resistance which has dietary implications and (2) circulating alanine aminotransferase (ALT) levels are reasonable markers predicting NAFLD status. In a recent cross-sectional study employing nondiabetic subjects, ALT values rose steadily within a normal range early in the life cycle but begin decreasing steadily around age 65 years.Objectives: Because of important nutritional implications, the association between ALT levels and aging in a significantly larger population of healthy volunteers was examined for corroborative purposes. A secondary goal was to gain further knowledge concerning mechanisms behind any age-related decline in ALT activity.Methods: Baseline data from over 10,000 physician-approved, nondiabetic subjects (age 21-84 years) of both genders who had volunteered for previous clinical investigations were assessed.Results: In this cross-sectional examination, the line of best fit (weighted) for average yearly circulating ALT levels displayed an upward surge from ages 21 to 64 years with a discernible steady downward decline around 65 years-mimicking earlier results. Examining linear lines of correlation in the younger and older age groups, the following calculations were determined: a significant positive slope for 21 to 64 years, r = 0.42, n = 44, p < 0.005, and a trending negative slope for 65 and beyond, r = -0.43, n = 20, p < 0.057. Using this same datum base, the correlations between age and fasting blood glucose (FBG) mimicked the ALT results by once more showing a similar upward rise in the younger and a steady decline the older group of volunteers.Conclusions: A paradoxical downward age-related (≥ 65 years) decline of circulating ALT coinciding with a comparable steady decrease in FBG levels was replicated in a larger population of volunteers. The close association of these two chemistries along with other findings suggest that altered glucose-insulin metabolism may participate via "survivor bias" in the ubiquitously found age-related decline of serum ALT-suggesting that nutritional measures could advance optimal health over the life-span.
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Envejecimiento/sangre , Envejecimiento/fisiología , Alanina Transaminasa/sangre , Fenómenos Fisiológicos de la Nutrición , Adulto , Anciano , Anciano de 80 o más Años , Glucemia , Presión Sanguínea , Composición Corporal , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
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Glucemia/fisiología , Ayuno/fisiología , Síndrome Metabólico , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Resistencia a la Insulina/fisiología , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered by some to be the hepatic manifestation of the metabolic syndrome (MS). However, others believe NAFLD is a distinct entity that actually initiates MS. Whichever is true, a definite linkage exists between both is generally accepted based upon the frequency of common occurrence and realization that insulin resistance (IR) is and realization that. The objective is to better understand the relationship between NAFLD and MS. Specifically, is there any concrete evidence that development of NAFLD precedes MS or vice versa? Another goal was to better comprehend capabilities of circulating aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and their ratio used commonly for diagnosis of NAFLD. METHODS: Data from 288 participants with fasting blood glucose (FBG) levels below the diabetic level (<125 mg/dL) and AST and ALT values in the normal range (<40 U/L) were examined. Correlations between ALT and AST and their ratio as independent variables with a variety of metabolic parameter were evaluated and compared. RESULTS: Like FBG, many significant positive correlations among glucose-insulin indices, body composition, blood pressure, dyslipidemias, and inflammation were discovered using ALT, and less so with AST, as the independent variable. In some cases, even stronger correlations in a negative direction with IR and MS were found with the ratio AST/ALT. Corroboration occurred when values in the lowest and highest quartiles of ALT and AST/ALT readings showed appropriate statistically significant differences. CONCLUSIONS: The findings here suggest that both NAFLD and the MS very early in development have a common inciting mechanism(s)-most likely IR. Accordingly, the early concurrent temporal results are consistent with the concept that NAFLD is a hepatic manifestation of the IR associated with the MS. They do not exclude the possibility that once some liver functional adjustments take place, several aspects of the MS are bolstered further, perhaps via intensified heightening of IR.
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Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Composición Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
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.
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Presión Sanguínea , Azúcares de la Dieta/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificación , Animales , Glucemia/metabolismo , Azúcares de la Dieta/efectos adversos , Modelos Animales de Enfermedad , Humanos , Hipertensión/epidemiología , Resistencia a la Insulina , Obesidad/epidemiología , Sobrepeso/epidemiología , Prevalencia , Cloruro de Sodio Dietético/efectos adversosRESUMEN
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.
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Envejecimiento/metabolismo , Glucosa/metabolismo , Resistencia a la Insulina , Síndrome Metabólico/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Presión Sanguínea , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , Estudios Transversales , Ayuno , Femenino , Humanos , Insulina/sangre , Recuento de Leucocitos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Triglicéridos/sangre , Adulto JovenRESUMEN
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.
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Extractos Vegetales/farmacología , Espermatozoides/efectos de los fármacos , Testosterona/sangre , Adulto , Afecto/efectos de los fármacos , Anciano , Sulfato de Deshidroepiandrosterona/sangre , Voluntarios Sanos , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Erección Peniana/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/fisiologíaRESUMEN
OBJECTIVES: Changes in body composition and blood chemistries between overweight adult subjects receiving a supplement containing either 3 g of konjac glucomannan/300 mg calcium carbonate or a placebo containing only 300 mg of calcium carbonate were compared as the primary objective. A secondary objective was to compare outcome differences between compliant and partially compliant subjects. METHODS: A total of 83 overweight adults (66 women and 17 men) completed a randomized, double-blind, placebo-controlled protocol in which they received either a glucomannan or placebo supplement for 60 days. Dual-energy x-ray absorptiometry (DEXA) total body scans and a 42-measurement blood test were completed at baseline and 60 days later. Compliance was assessed by rating self-reports of (1) how many tablets were taken, (2) adherence to taking the tablets 30 minutes before eating, and (3) a sum of the ratings for (1) and (2). An anonymous poststudy questionnaire and telephone calls were also completed by 80 (96%) of the participants who were used as the study cohort. RESULTS: No statistically significant differences were found between the groups on changes from baseline on the DEXA and blood tests. However, when subjects were classified as either compliant or partially compliant using the compliance measures, statistically significant reductions in scale weight, percentage body fat, fat mass, total cholesterol, and low-density lipoprotein (LDL) cholesterol were found in the glucomannan group compared to the placebo group. CONCLUSIONS: This study supports the efficacy glucomannan supplementation to reduce body weight, body fat, and circulating cholesterol levels without the concomitant loss of lean mass and bone density often associated with weight loss. However, these positive outcomes were not observable until corrections for compliance were applied.
RESUMEN
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.
Asunto(s)
Extractos Vegetales/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adolescente , Adulto , Femenino , Hormona Folículo Estimulante/sangre , Hemoglobinas/análisis , Humanos , Recuento de Leucocitos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Fitoterapia , Síndrome del Ovario Poliquístico/sangre , Trigonella , Adulto JovenRESUMEN
Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti-inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A. catechu heartwood extracts. Several studies have shown that a two-ingredient combination product containing A. catechu extract exhibited no adverse effects when administered daily for up to 12 weeks while exhibiting significant anti-inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety.
Asunto(s)
Acacia/química , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Analgésicos/farmacología , Animales , Antiinfecciosos/farmacología , Catequina/farmacología , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Placenta is an important organ that connects the developing fetus to allow nutrient uptake, antibody provisions and gas exchange via the blood supply of the mother. We developed a novel, standardized, stable, water-soluble, peptide-enriched hydrolyzed, Horus fermented placenta powder (HFPEP) from healthy, pathogen-free, swine placenta. Earlier studies demonstrated that HFPEP significantly improves physical fatigue, hepatic functions and repair of muscle fibers. We examined the broad safety of HFPEP in various toxicology models in Good Laboratory Practices-approved laboratories. The acute oral toxicity study was conducted in female Sprague-Dawley rats, and the acute oral LD50 was found to be greater than 5000 mg/kg body weight. Ames' bacterial reverse mutation assay was conducted to determine the ability of HFPEP to induce reverse mutation at selected histidine loci in five tester strains of Salmonella typhimurium viz. TA1535, TA1537, TA98, TA100 and TA102 in the presence and absence of a metabolic activation system (S9) at the doses of 50, 15, 4.5, 1.35 and 0.41 mg/ml. No mutagenic potential was observed. Mutagenic potential was also evaluated using in vivo micronucleus test, and no mutagenic potential of HFPEP was observed. Repeated dose 28-d oral toxicity study was performed in male and female rats with 14-d recovery period at the dose levels of 250, 500 or 1000 mg/kg. No abnormal clinical signs or toxicity were detected. No observed adverse effect level of HFPEP was found to be greater than 1000 mg/kg body weight. These studies affirm that HFPEP has broad spectrum safety for human consumption.
Asunto(s)
Fermentación , Péptidos/toxicidad , Extractos Placentarios/toxicidad , Administración Oral , Animales , Femenino , Dosificación Letal Mediana , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos , Mutación , Nivel sin Efectos Adversos Observados , Péptidos/administración & dosificación , Extractos Placentarios/administración & dosificación , Polvos , Ratas Sprague-Dawley , Medición de Riesgo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Porcinos , Factores de TiempoRESUMEN
The efficacy of a novel Prunus domestica bark extract (Sitoprin, CR002) was investigated on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in male Wistar rats. BPH was induced by daily subcutaneous administration of TP (3.0 mg/kg) over a period of 15 days (interim sacrifice group) and for an additional 21 days (terminal sacrifice group). We evaluated the dose-dependent efficacy (0, 50, 100 and 200 mg/kg body weight/day) of CR002 and a control group against BPH, and compared with a reference standard Prunus africana extract (CR001). Extensive clinical examinations were carried out on days 1, 7, 14, 21, 28 and 35 of treatment period to determine the onset, duration and severity of clinical signs. Clinical pathology, hematology, biochemistry and histopathology were performed on days 15 and 35, prior to necropsy. Animals were fasted overnight prior to blood collection. Prostate glands and tissues were examined. On day 36, histopathology of ventral prostrate of control rats demonstrates single layer of columnar mucin secreting epithelial cells along with a lumen occupied with eosinophilic secretion. In contrast, CR002 and CR001 groups (100 and 200 mg/kg/day) exhibited no hyperplasia and proliferation of epithelial cells. Prostate histopathology of these treated groups was comparable with control rats. The hyperplasia and hypertrophy of prostrate was reduced to single-layered cell indicating the efficacy of CR002 and CR001. Overall, results demonstrate that CR002 exhibits therapeutic efficacy/activity in TP-induced BPH in rats, which is comparable to CR001.