Role of Perivascular Adipose Tissue in Aorta Reactivity from Obese and Hyperglycemic CD-1 Mice: New Insights into Perivascular Adipose Tissue.

Background: Perivascular adipose tissue (PVAT) plays an essential role in cardiovascular homeostasis. However, during obesity and diabetes, its role in vascular tone regulation is unclear. This study aimed to evaluate the function of the PVAT on aorta reactivity in the lean and cafeteria (CAF) diet-induced obese-hyperglycemic mice model. Methods: Aorta reactivity to phenylephrine, KCl, and acetylcholine was analyzed in lean (n = 6) and obese mice (n = 6). Also, nitric oxide (NO-) and cyclooxygenase participation, in the presence (n = 6) and absence (n = 6) of PVAT, were examined in the aortas. Results: After a CAF diet for 19 weeks, obese mice showed increased body weight, glucose intolerance, and hypercholesterolemia concerning lean mice. Vascular reactivity to phenylephrine was reduced significantly in the aorta of obese mice. In contrast, the contraction produced by KCl (80 mM) was increased in the aorta of obese mice independent of PVAT. Acetylcholine-induced vasorelaxation diminished in the aortas of obese mice in the presence of PVAT. Nonselective inhibition of cyclooxygenases likely shows that PVAT and endothelium release vasorelaxant prostanoids. Conclusions: The results suggest that PVAT modulates aorta reactivity by releasing NO-, decreasing the α1-adrenergic response to phenylephrine, and probably releasing vasorelaxant prostanoids. The data suggest that PVAT regulates the vascular smooth muscle and endothelial function in a CAF diet-induced obese-hyperglycemic mice model.

Cannabis and cannabinoids as an alternative remedy in metabolic syndrome

Abstract Metabolic syndrome (MetS), an epidemic defined as a group of interconnected physiological, biochemistry, clinical, and metabolic factors, directly increases the risk of cardiovascular disease, atherosclerosis, type 2 diabetes, and death. MetS therapy includes diet, physical exercise, and a poly-pharmacological intervention. Cannabis is mainly recognized for its recreational uses and has several medical applications for neurological diseases, due to its hypnotic, anxiolytic, antinociceptive, anti-inflammatory, and anticonvulsant activities. Although several clinical observations in Cannabis smokers suggest metabolic effects, its utility in metabolic disorders is unclear. This review aims to determine under what conditions Cannabis might be useful in the treatment of MetS. Cannabis contains 120 phytocannabinoids, of which Δ9-THC mediates its psychoactive effects. Cannabinoids exert biological effects through interactions with the endocannabinoid system, which modulates several physiologic and metabolic pathways through cannabinoid receptors (CB1/CB2). Signaling through both receptors inhibits neurotransmitter release. In general, endocannabinoid system stimulation in Cannabis smokers and Δ9-THC signaling through CB1 have been implicated in MetS development, obesity, and type 2 diabetes. In contrast, CB1 antagonists and non-psychotropic phytocannabinoids like cannabidiol reduce these effects through interactions with both cannabinoid and non-cannabinoid receptors. These pharmacological approaches represent a source of new therapeutic agents for MetS. However, more studies are necessary to support the therapeutic potential of Cannabis and cannabinoids in metabolic abnormalities

GLUT4 translocation in C2C12 myoblasts and primary mouse hepatocytes by an antihyperglycemic flavone from Tillandsia usneoides.

BACKGROUND: Type 2 Diabetes (T2D) is characterized by deregulation in carbohydrate and lipid metabolism, with a very high mortality rate. Glucose Transporter type 4 (GLUT4) plays a crucial role in T2D and represents a therapeutic target of interest. Tillandsia usneoides (T. usneoides) is a plant used as a remedy for diabetes. T. usneoides decreased blood glucose in different experimental models. However, the involvement of GLUT4 in this effect has not yet been explored. PURPOSE: This study aimed to investigate whether any component in T. usneoides might participate in the effect on blood glucose through a bioassay-guided fractionation, testing its potential antihyperglycemic effect in mice, as well as its influence on GLUT4 translocation in C2C12 myoblasts and primary hepatocytes. METHODS: The aqueous extract and the Ethyl Acetate fraction (TU-AcOEt) of T. usneoides were evaluated in a hypoglycemic activity bioassay and in the glucose tolerance test in CD-1 mice. TU-AcOEt was fractionated, obtaining five fractions that were studied in an additional glucose tolerance test. C1F3 was fractioned again, and its fractions (C2F9-12, C2F22-25, and C2F38-44) were examined by HPLC. The C2F38-44 fraction was analyzed by Mass Spectrometry (MS) and subjected to additional fractionation. The fraction C3F6-9 was explored by Nuclear Magnetic Resonance (NMR), resulting in 5,7,4´-trihydroxy-3,6,3´,5´-tetramethoxyflavone (Flav1). Subsequently, a viability test was performed to evaluate the cytotoxic effect of Flav1 and fractions C2F9-12, C2F22-25. C2F38-44, and C3F30-41 in C2C12 myoblasts and primary mouse hepatocytes. Confocal microscopy was also performed to assess the effect of Flav1 and fractions on GLUT4 translocation. RESULTS: The TU-AcOEt fraction exhibited a hypoglycemic and antihyperglycemic effect in mice, and its fractionation resulted in five fractions, among which fraction C1F3 decreased blood glucose. MS and NMR analysis revealed the presence of Flav1. Finally, Flav1 significantly promoted the translocation of GLUT4 in C2C12 myoblasts and primary hepatocytes. CONCLUSION: To date, Flav1 has not been reported to have activity in GLUT4; this study provides evidence that T. usneoides is a plant with the potential to develop novel therapeutic agents for the control of T2D.

Jatropha Neopauciflora Pax Latex Exhibits Wound-Healing Effect in Normal and Diabetic Mice.

Jatropha neopauciflora is an endemic species of Mexico. Its latex is used to treat wounds, scarring, oral infections, and loose teeth. To date, there are no studies that validate at a morphological level a wound-healing use in diabetes. The present research aimed to evaluate the wound-healing capacity of the latex of J. neopauciflora in the skin of healthy and streptozotocin-induced diabetic mice. Also, a chemical analysis of the latex through molecular exclusion chromatography and HPLC were performed. Male mice (Mus musculus) of 7-week-old CD1 strain were used. Groups of healthy and diabetic mice were formed. A longitudinal cut of 1 cm was performed on the depilated skin. All treatments were topically applied to the wound area twice a day for ten days. At the end of the experiments, the skin sections were obtained from the wound area and stained with Hematoxylin-Eosin. Then we counted the number of active fibroblasts in all the experimental groups. In normal mice, the latex accelerated the wound-healing process and decreased the number of active fibroblasts, similarly to Recoveron. In diabetic mice, the latex and Recoveron increased the number of active fibroblasts. In normal and diabetic mice, a thin and orderly epidermis was observed. Molecular exclusion chromatography exhibited 58 fractions, 14 of which were subjected to HPLC, to detect catechin, a flavonoid with antioxidant, antimicrobial, and anti-inflammatory properties. J. neopauciflora latex can be useful for wound treatment in patients with diabetes mellitus because it accelerates and promotes the wound-healing process.

α-Amyrin induces GLUT4 translocation mediated by AMPK and PPARδ/γ in C2C12 myoblasts.

α-Amyrin, a natural pentacyclic triterpene, has an antihyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in insulin resistance (IR) and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along with adenosine-monophosphate (AMP) - activated protein kinase (AMPK) and protein kinase B (Akt), are implicated in translocation of glucose transporter 4 (GLUT4); however, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells. Our objective was to determine the action of α-amyrin in PPARδ, PPARγ, AMPK, and Akt in C2C12 myoblasts. The expression of PPARδ, PPARγ, fatty acid transporter protein (FATP), and GLUT4 was quantified using reverse transcription quantitative PCR and Western blot. α-Amyrin increased these markers along with phospho-AMPK (p-AMPK) but not p-Akt. Molecular docking showed that α-amyrin acts as an AMPK-allosteric activator, and may be related to GLUT4 translocation, as evidenced by confocal microscopy. These data support that α-amyrin could have an insulin-mimetic action in C2C12 myoblasts and should be considered as a bioactive molecule for new multitarget drugs with utility in T2D and other metabolic diseases.

Mechanism of the Hypoglycemic Activity and Hepatoprotective Effect of the Aqueous Extract of Cecropia obtusifolia Bertol.

In Central and South American traditional medicine, people use Cecropia obtusifolia Bertol (Cecropiaceae) for the treatment of diabetes mellitus. However, its hypoglycemic action mechanism at pancreatic and liver level has been poorly explored. The present research aimed to establish the influence of the aqueous extract of C. obtusifolia, standardized in its content of chlorogenic acid, on insulin secretion in RINm5F cells and over the liver carbohydrates and lipids metabolism, and to determine concomitantly its hepatoprotective effect on mice with streptozotocin-induced diabetes. In RINm5F cells, concentrations 5, 50, 100, and 200 µg/mL of aqueous extract of C. obtusifolia were used to determine [Ca2+]i and insulin secretion. In an acute study, the extract was administered at doses of 500 mg/kg. In another test (subacute), the extract was daily administrated to diabetic mice (200 mg/kg/day) for 30 days. Blood glucose levels and other biochemical parameters were determined, and a liver histological analysis was performed. In RINm5F cells, C. obtusifolia increased [Ca2+]i and insulin secretion, whereas in diabetic mice exhibited acute and subacute hypoglycemic effects. Daily administration of C. obtusifolia to diabetic mice also increased liver glycogen storage and glycogen synthase levels, without apparent changes in gluconeogenesis. Besides, it increased peroxisome proliferator-activated receptor-α (PPAR-α) and long-chain-fatty-acid-CoA ligase 1 (ACSL-1) expression and reduced triglycerides, transaminases (alanine aminotransferase and aspartate aminotransferase), and collagen fibers, modifying anti-inflammatory (adiponectin and interleukin-10) and inflammatory (tumor necrosis factor-α) cytokines in serum. Therefore, the hypoglycemic effect of C. obtusifolia implicates a dual action, promoting insulin secretion, liver glycogen accumulation, and hepatoprotection by decreasing collagen fibers and inflammatory markers, whereas it improves lipid metabolism, due in part to PPAR-α.

Ayahuasca: Uses, Phytochemical and Biological Activities.

Ayahuasca (caapi, yajé), is a psychoactive brew from the Amazon Basin region of South America traditionally considered a "master plant." It is prepared as a decoction from Banisteriopsis caapi and Psychotria viridis, which it is thought that it stimulates creative thinking and visual creativity. Native healers of the Orinoco and Amazon basins have used traditionally ayahuasca as a healing tool for multiple purposes, particularly to treat psychological disorders in the patients, with some beneficial effects experimentally and clinically validated. Recently, several syncretic religions, as the "União de Vegetal" (UDV) group in Brazil, have been spread around the world. The use of ayahuasca has been popularized by internet and smart-shops, bringing the psychoactive substance to new highs, emerging new "ayahuasqueros." Ayahuasca has alkaloids as ß-carbolines and dimethyltryptamines, which inhibit the monoamine oxidase and active the 5-HT2A (5-hydroxytryptamine) receptor, respectively, resulting in hallucinations in the users. Ayahuasca induces a psychedelic change in the anteroposterior coupling of the electrophysiological brain oscillations in humans. Traditional ayahuasca beverage is generating pharmacological, commercial and spiritual interest among the scientific community, government people, and different populations worldwide. The goal of this article is to report about the uses, chemistry and biological activities of ayahuasca.

Participation of the IKK-α/ß complex in the inhibition of the TNF-α/NF-κB pathway by glycine: Possible involvement of a membrane receptor specific to adipocytes.

Glycine modulates inflammatory processes mediated by macrophages and adipocytes through decreasing the secretion of TNF-α, IL-6, and leptin, while increasing adiponectin. These effects have been associated with the inactivation of NF-κB in response to TNF-α, across an increase of its inhibitor IκB-α in adipocytes. However, glycine upstream mainly influences the IκB kinase (IKK) complex, a multi-protein kinase complex considered a critical point in regulation of the NF-κB pathway; whether that is responsible for the TNF-α-induced phosphorylation of IkB has not been explored. Additionally, although previous studies have described glycine interactions with specific receptors (GlyR) in different immune system cell types, it is currently unknown whether adipocytes present GlyR. In this research, participation of the IKK-α/ß complex in the inhibition of the TNF-α/NF-κB pathway by glycine was evaluated and associated with the synthesis and secretion of inflammatory cytokines in 3T3-L1 adipocytes. Furthermore, we also explored GlyR expression, its localization on the plasmatic membrane, intracellular calcium concentrations [Ca2+]i and strychnine antagonist action over the GlyR in these cells. Glycine decreased the IKK-α/ß complex and the phosphorylation of NF-κB, diminishing the expression and secretion of IL-6 and TNF-α, but increasing that of adiponectin. GlyR expression and its fluorescence in the plasma membrane were increased in the presence of glycine. In addition, glycine decreased [Ca2+]i; whereas strychnine + glycine treatment inhibited the activation of NF-κB observed with glycine. In conclusion, the reduction of TNF-α and IL-6 and suppression of the TNF-α/NF-κB pathway by glycine may be explained in part by inhibition of the IKK-α/ß complex, with a possible participation of GlyR in 3T3-L1 adipocytes.

Potential of the chlorogenic acid as multitarget agent: Insulin-secretagogue and PPAR α/γ dual agonist.

The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca2+]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200µM of CGA showed an increase in [Ca2+]i of 9-times versus control and 4-times as compared to positive control; in addition, an increase in insulin secretion was observed similarly to those of positive control. CGA also significantly increased the mRNA expression of PPARγ (150%) and GLUT4 (220%), as well PPARα (40%) and FATP (25%) as it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested that CGA has suitable physicochemical properties to be considered as leader bioactive molecule for the development of novel agents with similar properties. Together, our results indicate that CGA possesses multiple mechanisms of action for the development of highly effective therapeutics in the treatment of metabolic diseases such as type 2 diabetes.

Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats.

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies. Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10µM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p<0.05) were diminished. Moreover, IL-1ß and IL-18 expression was significantly decreased in adipose tissue (p<0.05); meanwhile adiponectin was significantly overexpressed (p<0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p<0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p<0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.

Cucurbita ficifolia Bouché increases insulin secretion in RINm5F cells through an influx of Ca(2+) from the endoplasmic reticulum.

ETHNOPHARMACOLOGICAL IMPORTANCE: Cucurbita ficifolia Bouché(C. ficifolia) is a plant used in Mexican traditional medicine to control type 2 diabetes (T2D). The hypoglycemic effect of the fruit of C. ficifolia has been demonstrated in different experimental models and in T2D patients. It has been proposed that D-chiro-inositol (DCI) is the active compound of the fruit. Additionally, it has been reported that C. ficifolia increases the mRNA expression of insulin and Kir 6.2 (a component of the ATP-sensitive potassium (K(+)ATP) channel, which is activated by sulphonylurea) in RINm5F cells. However, it remains unclear whether C. ficifolia and DCI causes the secretion of insulin by increasing the concentration of intracellular calcium ([Ca(2+)]i) through K(+)ATP channel blockage or from the reservoir in the endoplasmic reticulum (ER). MATERIAL AND METHODS: The aqueous extract of C. ficifolia was obtained and standardized with regard to its DCI content. RINm5F pancreatic ß-cells were incubated with different concentrations (50, 100, 200 and 400µM) of DCI alone or C. ficifolia (9, 18, 36 and 72µg of extract/mL), and the [Ca(2+)]i of the cells was quantified. The cells were preloaded with the Ca(2+) fluorescent dye fluo4-acetoxymethyl ester (AM) and visualized by confocal microscopy. Insulin secretion was measured by an ELISA method. Subsequently, the effect of C. ficifolia on the K(+)ATP channel was evaluated. In this case, the blocker activator diazoxide was used to inhibit the C. ficifolia-induced calcium influx. In addition, the inositol 1,4,5-trisphosphate (IP3)-receptor-selective inhibitor 2-amino-thoxydiphenylborate (2-APB) was used to inhibit the influx of calcium from the ER that was induced by C. ficifolia. RESULTS: It was found that DCI alone did not increase [Ca(2+)]i or insulin secretion. In contrast, treatment with C. ficifolia increased [Ca(2+)]i 10-fold compared with the control group. Insulin secretion increased by 46.9%. In the presence of diazoxide, C. ficifolia decreased [Ca(2+)]i by 50%, while insulin secretion increased by 36.4%. In contrast, in the presence of 2-APB, C. ficifolia increased [Ca(2+)]i 18-fold, while insulin secretion remained constant, indicating an additive effect. Therefore, C. ficifolia was not found to block the K(+)ATP channel. However, it did exert an effect by increasing [Ca(2+)]i from the ER, which may partly explain the insulin secretion observed following treatment with C. ficifolia. CONCLUSIONS: The hypoglycemic properties of C. ficifolia can be explained in part by its effect as a secretagogue for insulin through an increase in [Ca(2+)]i from the calcium reservoir in the ER. Therefore, the mechanism of action of C. ficifolia is different to those of the currently used hypoglycemic drugs, such as sulfonylureas. These results support that C. ficifolia may be a potential natural resource for new agents to control T2D.

Synthesis, in vitro and in silico studies of a PPARγ and GLUT-4 modulator with hypoglycemic effect.

Compound {4-[({4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}acetyl)amino]phenoxy}acetic acid (1) was prepared and the in vitro relative expression of PPARγ, GLUT-4 and PPARα, was estimated. Compound 1 showed an increase of 2-fold in the mRNA expression of PPARγ isoform, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus (NIDDM) rat model. The in vivo results indicated a significant decrease of plasma glucose levels, during the 7 h post-administration. Also, we performed a molecular docking of compound 1 into the ligand binding pocket of PPARγ, showing important short contacts with residues Ser289, His323 and His449 in the active site.

Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa.

Effect of fructooligosaccharides fraction from Psacalium decompositum on inflammation and dyslipidemia in rats with fructose-induced obesity.

Psacalium decompositum, commonly known as "Matarique," is a medicinal plant used in Mexico for diabetes mellitus empirical therapy. Previous studies have shown that the fructooligosaccharides (FOS) present in the roots of this plant exhibit a notable hypoglycemic effect in animal models; this effect might be associated with the attenuation of the inflammatory process and other metabolic disorders. In this study, we examined the effects of FOS fraction administration in a fructose-fed rat model for obesity. Phytochemical chromatographic studies (high performance thin layer chromatography and nuclear magnetic resonance) were performed to verify isolation of FOS. 24 male Wistar rats were maintained for 12 weeks on a diet of 20% HFCS in drinking water and chow. Glucose, cholesterol, triglycerides and liver transaminases levels were measured monthly, after administering FOS fraction intragastrically (150 mg/kg/day for 12 weeks), while the levels of inflammatory cytokines were only quantified at the end of the treatments. Rats treated with FOS fraction decreased body weight, cholesterol, triglycerides, and significantly reduced IL-6, IFN-γ, MCP-1, IL-1ß and VEGF levels (p < 0.05). These results suggest that P. decompositum has anti-inflammatory and hypolipidemic properties that might be used as an alternative treatment for the control of obesity.

Cucurbita ficifolia†Bouché (Cucurbitaceae) and D-chiro-inositol modulate the redox state and inflammation in 3T3-L1 adipocytes.

OBJECTIVES: Cucurbita ficifolia (characterised by its D chiro inositol (DCI) content) and of synthetic DCI on the redox state, mRNA expression and secretions of proinflammatory cytokines. Additionally, we evaluated the insulin-mimetic action of both treatments by assessing protein kinase B (PKB) activation in 3T3-L1 adipocytes. METHODS: Adipocytes were treated with C. ficifolia and synthetic DCI. The redox state was determined by spectrophotometry as changes in the reduced glutathione/oxidised glutathione (GSH/GSSG) ratio, glutathione peroxidase and glutathione reductase activities; H2 O2 levels were measured by flow cytometry. The mRNA expression and the protein level of cytokines were determinate by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activation of PKB activation was detected by Western blot. KEY FINDINGS: C. ficifolia extract and synthetic DCI reduced oxidative stress by decreased H2 O2 levels, increased glutathione peroxidase activity and changes in the GSH/GSSG ratio. Furthermore, DCI decreased the mRNA expression and secretion of tumour necrosis factor-α, interleukin 6 (IL-6) and resistin, while C. ficifolia reduced protein levels of resistin and increased IL-6 levels. Only DCI demonstrated insulin-mimetic action. CONCLUSIONS: The antioxidant and anti-inflammatory effects of C. ficifolia extract can be explained in part by its DCI content, which modulates the GSH/GSSG ratio and contributes to a reduced proinflammatory state. C. ficifolia and DCI treatments may reduce the disturbances caused by oxidative stress. Additionally, DCI may improve insulin sensitivity through its insulin-mimetic effects.

Influence of two hypoglycemic Cucurbitaceae (Cucurbita ficifolia Bouché and Ibervillea sonorae Greene) on ATP-sensitive potassium channels in rat aortic rings / Influencia de dos Cucurbitaceae (Cucurbita ficifolia Bouché e Ibervillea sonorae Greene) sobre los canales de potasio sensibles a ATP en anillos aórticos de rata

Cucurbita ficifolia Bouché fruit containing D-chiro-inositol and Ibervillea sonorae Greene root containing cucurbitane-type glycosides are used to control diabetes in Mexico. Although the hypoglycemic effect of both plants has been demonstrated and some active compounds proposed, their mechanisms are still unknown. The aim of this study was to determine if the incubation with both aqueous extracts avoids the inhibition of contraction induced by phenylephrine similarly to glibenclamide in rat aortic rings. The hypoglycemic aqueous extracts of C. ficifolia and I. sonorae were characterized for their content of either D-chiro inositol or cucurbitanes respectively, and then we assayed the characterized extracts in vitro on the diazoxide-induced relaxation of rat aortic rings precontracted with phenylephrine, using as positive control glibenclamide. I. sonorae extract blocked the KATP channels in a concentration-dependent manner (p < 0.05), whereas C. ficifolia extract had no effect on these channels. I. sonorae extract produces a hypoglycemic effect through a similar mechanism to sulphonylureas in this experimental model; however, hypoglycemic action of C. ficifolia extract should be explained by an independent KATP channels mechanism.

Los frutos de Cucurbita ficifolia conteniendo D-quiro-inositol y las raíces de Ibervillea sonorae conteniendo glucósidos tipo cucurbitano son empleados en el control de la diabetes en México. Aunque el efecto hipoglucémico de ambas plantas ha sido demostrado y se han propuesto algunos de sus compuestos activos, aún se desconoce su mecanismo de acción. El objetivo de este estudio fue determinar si la incubación con ambos extractos acuosos evita la inhibición de la contracción inducida por fenilefrina de manera similar a la glibenclamida en anillos aórticos de rata. Los extractos acuosos hipoglucémicos de C. ficifolia e I. sonorae fueron caracterizados en su contenido de D-quiro inositol o cucurbitanos, respectivamente y entonces fueron estudiados en un modelo in vitro en la relajación inducida por diazóxido en anillos aórticos previamente contraídos con fenilefrina, usando como control positivo glibenclamida. El extracto de Ibervillea sonorae bloqueó los canales KATP de manera dosis-dependiente (p < 0.05), mientras que Cucurbita ficifolia no tuvo efecto en esos canales. El extracto de I. sonorae produce efecto hipoglucémico a través de un mecanismo similar al de las sulfonilureas en este modelo experimental; por su parte, la acción hipoglucemiante del extracto de C. ficifolia debe ser explicado mediante un mecanismo independiente de los canales KATP.

Chemical characterization and evaluation of the hypoglycemic effect of fructooligosaccharides from Psacalium decompositum.

Psacalium decompositum (Gray) H.E. Rob. & Brett (Asteraceae), popularly known as "matarique," is a medicinal plant used in Mexico for the empirical treatment of diabetes mellitus. Previous studies with P. decompositum roots demonstrated that an aqueous fraction containing carbohydrates (WMP-fraction) exhibited a notable hypoglycemic effect in experimental animals. However, studies to identify these carbohydrates have not yet been performed. The goal of this investigation was to isolate and characterize the principal compounds in the WMP-fraction by spectroscopic and spectrometric analysis. Additionally, we sought to evaluate the hypoglycemic effect of these compounds in healthy and alloxan-induced diabetic mice. The results show that the chemical structures of the major compounds in the WMP-fraction correspond with fructan-type oligosaccharides and have a hypoglycemic effect in healthy and diabetic mice.

La obesidad como un proceso inflamatorio / Obesity as an inflammatory process

La obesidad es un problema muy importante a nivel mundial que ha aumentado rápidamente, alcanzando características de pandemia. En los últimos años se ha observado que los pacientes obesos presentan un estado inflamatorio crónico de bajo grado como una consecuencia del incremento en la masa del tejido adiposo, que lleva a un aumento en la producción de mediadores proinflamatorios que son conjuntamente estimulados por señales de origen exógeno y/o endógeno. El tejido adiposo contiene fibroblastos, preadipocitos, adipocitos y macrófagos; estos últimos contribuyen de manera importante al proceso inflamatorio sistémico con la producción de mediadores proinflamatorios. Así, existe una asociación íntima, altamente coordinada, entre las vías inflamatorias y las metabólicas; destaca la coincidencia en las funciones de los macrófagos y los adipocitos en la obesidad. Dilucidar los vínculos que existen entre obesidad e inflamación es de importancia capital dentro del campo de la biología molecular; esto implica el reconocimiento de las adipocinas, moléculas sintetizadas por los adipocitos, para dar lugar al descubrimiento de nuevos blancos terapéuticos relacionados con la inmunidad y el metabolismo, y de esta manera abrir la posibilidad de frenar la evolución de los procesos inflamatorios que culminan en enfermedades degenerativas.

Obesity is a major problem worldwide whose prevalence is increasing rapidly, with characteristics of a pandemic. In recent years it has become clear that obese patients present a low-grade chronic inflammation as a result of increased fat tissue and, consequently, an increased production of proinflammatory mediators by exogenous or endogenous stimuli. Fat tissue contains fibroblasts, preadipocytes, adipocytes and macrophag-es with the latter contributing to the systemic inflammatory process in the production of proinflammatory mediators. Thus, there is a highly coordinated intimate association between inflammatory and metabolic pathways, highlighting the overlap between the functions of macrophages and adipocytes in obesity. Elucidating the links between obesity and inflammation is of primordial importance within the field of molecular biology of obesity, which implies the recognition of adipokines, molecules synthesized by adipocytes, which may lead to the discovery of new therapeutic targets related to metabolism and immunity. This may open the possibility to halt the development of inflammatory processes leading to degenerative diseases.

[Leptin and its association with obesity and type 2 diabetes]. / Leptina y su relación con la obesidad y la diabetes mellitus tipo 2.

The number of patients with metabolic disorders, obesity, type 2 diabetes and hypertension is increasing worldwide. The increase in body weight as a consequence of genetic, environmental, and nutritional factors contributes to these disorders, playing a significant role in their disease course. In 1994 the obesity gene (ob) which encodes a protein named leptin, considered an important molecule in regulation of body weight, was described Body weight gain has been generally correlated with high plasma levels of leptin, generating a state of leptin-resistance. Because of its association with obesity, leptin has also been connected with type 2 diabetes and insulin-resistance, an essential characteristic of this disease. Leptin has also been linked with other disorders such as dyslipidaemia, and cardiovascular disease (conditions that together are known as metabolic syndrome), as well as cancer, psychological deficits, sexual dysfunction, etc. We describe some important biochemical and molecular aspects associated with the physiology of leptin, emphasizing the pathological consequences associated with obesity and diabetes.

Leptina y su relación con la obesidad y la diabetes mellitus tipo 2 / Leptin and its association with obesity and type 2 diabetes

En los últimos años, el número de pacientes con alteraciones metabólicas, tales como obesidad, diabetes mellitus tipo 2, hipertensión, etcétera, se ha incrementado. El aumento en el peso corporal, resultante de los factores genéticos, ambientales y nutricionales, tiene un papel muy importante en el desarrollo de diversas alteraciones metabólicas. En 1994 se describió al gen de la obesidad (ob) que codifica para la proteína leptina, molécula importante en la regulación del peso corporal. La ganancia en el peso normalmente correlaciona con un incremento de la proteína leptina, generándose a largo plazo un estado de resistencia a la misma. Además de esta relación con la obesidad, la leptina también se ha asociado con la diabetes mellitus tipo 2 y con la resistencia a la insulina, característica principal de esta patología. La leptina también se ha relacionado con otras enfermedades tales como cáncer, trastornos psicológicos y sexuales, entre otros. En este trabajo se analizan algunos aspectos bioquímicos y moleculares relacionados con la fisiología de la leptina; se hace énfasis en las consecuencias patológicas que causan su desregulación en la obesidad y la diabetes mellitus tipo 2.

The number of patients with metabolic disorders, obesity, type 2 diabetes and hypertension is increasing worldwide. The increase in body weight as a consequence of genetic, environmental, and nutritional factors contributes to these disorders, playing a significant role in their disease course. In 1994 the obesity gene (ob) which encodes a protein named leptin, considered an important molecule in regulation of body weight, was described Body weight gain has been generally correlated with high plasma levels of leptin, generating a state of leptin-resistance. Because of its association with obesity, leptin has also been connected with type 2 diabetes and insulin-resistance, an essential characteristic of this disease. Leptin has also been linked with other disorders such as dyslipidaemia, and cardiovascular disease (conditions that together are known as metabolic syndrome), as well as cancer, psychological deficits, sexual dysfunction, etc. We describe some important biochemical and molecular aspects associated with the physiology of leptin, emphasizing the pathological consequences associated with obesity and diabetes.