Ethanolic extract of Lippia graveolens stem reduce biochemical markers in a murine model with metabolic syndrome.

Metabolic Syndrome (MetS) is a risk to develop metabolic-chronic degenerative disease, it is important to find natural alternatives to help decrease the risk. Mexican oregano has a traditional use in Mexican food, moreover, has pharmacologic effects that can help to reduce risk the metabolic syndrome. The aim of this work was to determine the effect of Mexican oregano ethanolic extract in metabolic syndrome in murine model. Ethanolic extract of Mexican oregano (Lippia graveolens) stem (Ext) had a favorable effect on biochemical markers in a murine model of MetS, induced by injection of monosodium glutamate (MSG). From newborn female mice, two groups were formed: control and the MSG groups, which received a dosage of 2 mg/kg of MSG via subcutaneous injection at the second and fourth postnatal day (PD 2,4), and 4 mg/kg at the PD 6, 8, 10 to induce obesity. On week 13, a part of the MSG group received Ext (group MSG + Ext) at 300 mg/kg, administered orally daily from week 13 to week 18. The results indicated that ethanolic extract of Lippia graveolens stem decreases the percentage of body fat, waist circumference, and body weight gain as well as cholesterol, serum triglyceride concentrations and systolic and diastolic pressure. Insulin and leptin hormone values showed a significant effect with the Ext administration. However, hepatic lipoperoxidation levels of MSG and MSG + Ext groups did not show any statistically significant differences between them, both being higher than the control group. Taking in consideration the results obtained in this study, it is concluded that the administration of Ext had a beneficial effect in the murine model with MetS. This is the first study demonstrating the potential of the polar fraction Lippia graveolens stem in MetS.

The Nutraceutical Antihypertensive Action of C-Phycocyanin in Chronic Kidney Disease Is Related to the Prevention of Endothelial Dysfunction.

C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction.

Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla.

Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE) and organic extract (OE). The OE has the highest amount of phenols (724.1 ± 12.0 GAE/g). Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC); OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets.

Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity.

Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, ß-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.

Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death.

Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA-neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells.

Exploring the structure and conformational landscape of human leptin. A molecular dynamics approach.

Leptin is a hormone that regulates energy homeostasis, inflammation, hematopoiesis and immune response, among other functions (Houseknecht et al., 1998; Zhang et al., 1995; Paz-Filho et al., 2010). To obtain its crystallographic structure, it was necessary to substitute a tryptophan for a glutamic acid at position 100, thus creating a mutant leptin that has been reported to have biological activity comparable to the activity of the wild type but that crystallizes more readily. Here, we report a comparative study of the conformational space of WT and W100E leptin using molecular dynamics simulations performed at 300, 400, and 500 K. We detected differences between the interactions of the two proteins with local and distal effects, resulting in changes in the conformation, accessible surface area, compactness, electrostatic potential and dynamic behavior. Additionally, the series of unfolding events that occur when leptin is subjected to high temperature differs for the two constructs. We observed that both proteins are mostly unstructured after 20 ns of MD simulation at 500 K. However, WT leptin maintains a significant amount of secondary structure in helix α2, while the most stable region of W100E leptin is helix α3. Furthermore, we found that the region between residues 25 and 42 might adopt interconverting secondary structures ranging from α-helices and random coils to ß-strand structures. Thus, this region can be considered an intrinsically disordered region. This atomistic description supports our understanding of leptin signaling and consequently might facilitate the use of leptin in treatments for the pathophysiologies in which it is implicated.

Pharmacological and Genotoxic Properties of Polyphenolic Extracts of Cedrela odorata L. and Juglans regia L. Barks in Rodents.

Evaluation of the phenolic compounds and antioxidant activity of Cedrela odorata L. and Juglans regia L. bark extracts was performed in vitro. Juglans regia showed greater extract concentration and higher antioxidant activity. Hypoglycemic activity in rats was assessed by generating a glucose tolerance curve and determining the area under the curve (AUC). Diabetes was later induced by an injection with streptozotocin (65 mg/kg of b.w.) and confirmed after 24 hours. The extract was administered (200 mg/kg b.w.) over 10 days, and blood glucose was monitored and compared with a control group. The glucose AUC showed a hypoglycemic effect of J. regia and C. odorata in normal rats. Both extracts reduced hepatic lipid peroxidation in diabetic rats. Polyphenolic extracts reduced cholesterol levels in a hypercholesterolemic mouse model and decreased hepatic lipid peroxidation. Polyphenolic extract doses of 100 and 200 mg/kg b.w. were administered alone or with cyclophosphamide (CPA) 50 mg/kg ip, which was used as a positive control. Analyses were performed using leukocytes in a comet assay after 4 and 24 h of treatment. Genotoxic effects were evaluated by the comet assay, which showed that while J. regia extract had no effect, C. odorata extract induced slight damage at 200 mg/kg, with the formation of type 0 and 1 comets.

The long-term ingestion of a diet high in extra virgin olive oil produces obesity and insulin resistance but protects endothelial function in rats: a preliminary study.

BACKGROUND: It has been hypothesized that fatty acids derived from a diet high in saturated fat may negatively affect endothelial function more significantly than a diet high in unsaturated fat; nevertheless, the effects of the long-term ingestion of monounsaturated fatty acids on endothelial function have been poorly studied. METHODS: To examine the chronic effects of monounsaturated (e.g., extra virgin olive oil (EVOO)) or saturated (e.g., margarine (M)) fatty acid-rich diets on the development of insulin resistance and endothelial dysfunction in rats, three groups of rats were fed control, high-EVOO or high-M diets for 20 weeks. Body weight, energy consumption, insulin resistance, lipid peroxidation and in vitro vascular reactivity with and without metformin were assessed during the study period. RESULTS: Both high-fat diets produced obesity and insulin resistance. EVOO-fed rats showed smaller increases in total cholesterol and arterial lipid peroxidation when compared with M-fed rats. Vascular reactivity to phenylephrine and sodium nitroprusside was not modified, but the vasodilating effect of carbachol was especially reduced in the M-fed rats compared with the EVOO-fed or control groups. Metformin addition to the incubation media decreased the vascular response to phenylephrine; decrease that was lower in rats fed with both high fat diets, and increased the carbachol and nitroprusside effects, but the metformin-enhanced response to carbachol was lower in the M group. CONCLUSIONS: Our results suggest that feeding rats with high quantities of EVOO, despite producing obesity and insulin resistance, produces low levels of circulating cholesterol and arterial lipoperoxidation compared to M fed rats and shows a preserved endothelial response to carbachol, effect that is significantly enhanced by metformin only in rats fed with control and EVOO diets.

Association of the polymorphisms 292 C>T and 1304 G>A in the SLC38A4 gene with hyperglycaemia.

BACKGROUND: The SLC38A4 gene is related to system 'A' activity, which seems to be related to impaired gluconeogenesis. The objective of this study was to determine whether the 292 C>T and 1304 G>A polymorphisms of SLC38A4 gene are associated with hyperglycaemia in humans. METHODS: A total of 227 individuals were enrolled in a case-control study, in which hyperglycaemia was defined by plasma glucose levels ≥95 mg/dL. Genotyping was carried out by using real-time polymerase chain reaction. RESULTS: The frequency of mutant alleles of SLC38A4 gene for single-nucleotide polymorphism (SNP) 1304 G>A was 23.6% and 30.2% for SNP 292 C>T. The frequency of allele T for the SNP 292 C>T in the case and control groups did not show significant differences, whereas the frequency of allele A for the SNP 1304 G>A was significantly higher in the case group than in the control group (p = 0.04). In the logistic regression analysis, the SNP 1304 G>A [odds ratio (OR) 1.78; 95%CI 1.04-3.05, p = 0.03] but not SNP 292 C>T (OR 1.41; 95%CI 0.80-2.47, p = 0.23) showed a significant association with hyperglycaemia. After adjusting by body mass index, waist circumference and triglycerides, the SNP 1304 G>A remained significantly associated with hyperglycaemia (OR 2.13; 95%CI 1.18-3.83, p = 0.03). Pair wise linkage disequilibrium showed correlation (D' > 0.82) between 292 C>T and 1304 G>A SNPs. Haplotype association with hyperglycaemia also showed significant association between both homozygous mutant alleles (A/T) and hyperglycaemia (OR 1.68; 95%CI 1.01-2.79, p = 0.048). CONCLUSIONS: Our results suggest that mutant allele A for SNP 1304 G>A of SLC38A4 gene is associated with hyperglycaemia.

Spirulina (arthrospira) protects against valproic acid-induced neural tube defects in mice.

Valproic acid (VPA) is a potent inducer of neural tube defects in human and mouse, its teratogenicity is associated with its potential to generation of free radicals and increase oxidative stress. Furthermore, spirulina (SP) has shown pharmacological properties against teratogenicity, which are attributed to its antioxidant potential. Accordingly, the present study was performed to investigate the influence of SP on the teratogenicity of VPA in imprinting control region mice and the possible mechanisms of action. VPA (sodium valproate) was administered intraperitoneally to mice on gestation day (GD) 8 at a dose of 600 mg/kg. SP was given orally at 125, 250, and 500 mg/kg daily from GD0 through GD18. The most common finding in fetuses with VPA exposure was exencephaly. SP decreased the incidence of this and other malformations and increased levels of superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, these results illustrate the protective action of SP through its antioxidant activity against VPA-induced teratogenicity.

Antiobesity and hypoglycaemic effects of aqueous extract of Ibervillea sonorae in mice fed a high-fat diet with fructose.

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported that Ibervillea sonorae had hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueous I. sonorae extract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment with I. sonorae aqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract from I. sonorae root prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity.

Spirulina (Arthrospira) protects against cadmium-induced teratogenic damage in mice.

The role of Spirulina (Arthrospira) in preventing cadmium (Cd) teratogenicity in ICR mice was studied. Cd was administered intraperitoneally to female mice at 1.5 mg/kg on gestation day (GD)-7, and Spirulina was given by peroral (intragastric) administration at 62.5, 125, 250, or 500 mg/kg from GD-0 through GD-17 (the day when animals were sacrificed). Because among the mechanisms suggested to account for reproductive damage are oxidative stress and lipoperoxidation, embryonic hydroperoxides were also determined. Treatment with Spirulina at the three highest doses significantly decreased the frequency of fetuses with exencephaly, micrognathia, and skeletal abnormalities induced by Cd. Furthermore, Spirulina treatment significantly and dose-dependently decreased lipid peroxidation, which was dramatically increased by administration of the metal. The results of the present study clearly point to the therapeutic potential of Spirulina in Cd-induced teratogenicity and probably through its antioxidant activity.

Protection against cadmium-induced teratogenicity in vitro by glycine.

Cadmium (Cd) has an embryotoxic effect on laboratory animals expressed by growth retardation and induced craniofacial and skeletal malformations. Some of the mechanisms suggested to account for this reproduction damage include oxidative stress and lipoperoxidation. It has been shown that due to its antioxidant activity, glycine protects embryos from in vivo cadmium-induced teratogenicity. However, it is not known whether such protection may also be found in embryo cultures and what its possible mechanism of action might be. The purpose of this study was to determine whether the effect of glycine (1 mM) against the damage of CdCl(2) (1 microM) on the embryo, was direct or indirect. The amino acid was found to have significantly counteracted the effects of Cd by reducing the growth retardation and preventing the opening of the neural tube. Such protective effect seems to be partly due to decreased lipoperoxidation levels in embryos exposed to the metal, which would make it a direct effect.

Glycine reduces cadmium-induced teratogenic damage in mice.

The effect of glycine in preventing cadmium (Cd) teratogenicity in mice was studied. Cadmium chloride (CdCl2) was administered subcutaneously at 1, 2 or 4 mg/kg doses on gestation days (GD) 7, 8 and 9. Glycine was given ad libitum (in the drinking water) from GD0 through GD18 (the day when animals were killed), as a 1% and 2% drinking water solution. Cd and nucleic acid concentrations in embryos were determined. The most common finding seen after CdCl2 4 mg/kg exposure was exencephaly. The incidence of this malformation was significantly reduced in mice receiving 2% glycine while fetal Cd significantly decreased as compared to cadmium-treated positive control animals. Increased nucleic acid levels were seen in the same embryos. In glycine non-supplemented mice given CdCl2 4 mg/kg, embryonic lipid peroxidation proved to be increased. In conclusion, lipid peroxidation was associated with cadmium-induced teratogenicity, and glycine inhibited the cadmium-induced effect by inhibiting placental transport of cadmium. However, further detailed studies are needed to establish the mechanism(s) of action.