F.J. Alarcon-Aguilar

Anti-hyperglycemic effect of some edible plants

The anti-hyperglycemic effect of 12 edible plants was studied on 27 healthy rabbits, submitted weekly to subcutaneous glucose tolerance tests after gastric administration of water, tolbutamide or a traditional preparation of the plant. Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha, Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak. Brassica oleracea var. botrytis, Allium cepa and Allium sativum only decrease the hyperglycemic peak. The glycemic decreases caused by Psidium guajava, Brassica oleracea and Lactuca sativa var. romana were not significant (P > .05). The integration of a menu that includes the edible plants with hypoglycemic activity for the control and prevention of diabetes mellitus may be possible and recommendable.

Hypoglycemic effect of extracts and fractions from Psacalium decompositum in healthy and alloxan-diabetic mice

The hypoglycemic effect of the hexane, methanol and water extracts obtained from roots of Psacalium decompositum (Asteraceae) was investigated in fasting healthy mice. Only the water extract significantly reduced blood glucose in a dose-dependent manner in normal mice after intraperitoneal administration (P<0.05). This water extract was macerated with methanol obtaining a precipitate (WMP fraction), and it was studied in healthy and alloxan-diabetic mice. The WMP fraction showed significant hypoglycemic activity in healthy and mild diabetic mice, but the administration of this fraction to animals with severe diabetes did not cause any significant decrease in blood glucose levels. Two polysaccharide components isolated from WMP fraction showed hypoglycemic effect when tested in healthy mice.

Effect of a Polyphenol-Rich Extract from Aloe vera Gel on Experimentally Induced Insulin Resistance in Mice

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.

Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cells

Obesity and type 2 diabetes course with chronic low-grade inflammation, where adiponectin is down-regulated and pro-inflammatory markers, like interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP), are up-regulated. A treatment option to improve the micro- and macro-complications in type 2 diabetes is the use of glycine, which has been demonstrated previously to increase the expression of anti-inflammatory cytokine IL-10 in monocytes and down-regulate the expression of TNF-alpha in monocytes and Kupffer cells. Recently, our group demonstrated that glycine decreases the pro-inflammatory plasmatic cytokines in type 2 diabetes. The aim of this study was to test the effect of glycine on adipokines expression in 3T3-L1 cells. Cells were grown and differentiated in the presence of 10 mM glycine. After 2 days of confluence, cells were differentiated to adipocytes in the same medium supplemented with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine. The RNA was extracted at days 0 and 8 of differentiation (fibroblasts and mature adipocyte phenotypes, respectively). The expression of PPAR-gamma (peroxisome proliferator-activated receptor-gamma), adiponectin, resistin, IL-6 and TNF-alpha were analyzed by real-time PCR. We demonstrated that when 3T3-L1 cells were treated with glycine, IL-6, resistin and TNF-alpha mRNA expression was decreased, but surprisingly adiponectin and PPAR-gamma were up-regulated. In all cases the values were statistically significant (P<0.05) between glycine treatment and controls. These results show that glycine improves the pro-inflammatory profile and up-regulates adiponectin gene expression. Therefore, glycine could be useful as a modulator of the pro-inflammatory state observed in obesity and type 2 diabetes.

Effects of three Mexican medicinal plants (Asteraceae) on blood glucose levels in healthy mice and rabbits

The effects of Psacalium decompositum, Psacalium peltatum and Acourtia thurberi (Asteraceae) on blood glucose levels were investigated in fasting mice and temporally hyperglycemic rabbits. The root decoction of P. decompositum reduced the blood glucose of normal mice from 49.1 +/- 3.8 to 35.7 +/- 2.0 mg/dl after intraperitoneal administration (P < or = 0.005) and significantly lowered the hyperglycemic peak (17.1%) in rabbits with temporal hyperglycemia. P. peltatum and A. thurberi decoctions also diminished fasting glycemia in mice and hyperglycemia in rabbits, but the effects were minor. A preliminary phytochemical study using thin layer chromatography showed that water decoctions of the three roots contained alkaloids and sugars. P. decompositum and P. peltatum showed the presence of maturine. However, other furoeremophylanes, such as cacalol and cacalone were only present in P. decompositum. A. thurberi root water decoction showed the presence of the benzoquinone perezone, and its derivative pipitzol.

Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice

Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.

Evaluation of the hypoglycemic effect of Cucurbita ficifolia Bouché (Cucurbitaceae) in different experimental models

Acute hypoglycemic effects of freeze-dried juice of Cucurbita ficifolia Bouché (Cucurbitaceae) fruits were studied in healthy and alloxan-diabetic mice. C. ficifolia fruit administered by intraperitoneal route produced, in a dose-dependent manner, a significant decrease of the glycemia in healthy mice. Although oral route of C. ficifolia fruit juice also caused significant reductions of blood glucose levels in healthy mice, the effect was minor. The juice administered by intraperitoneal route showed an acute hypoglycemic effect in alloxan-diabetic mice. In addition, daily oral administration of this preparation showed a highly significant reduction of the glycemia after 14 days of treatment. Freeze- dried juice caused acute toxicity when administered intraperitoneally, and also when it was administered daily by the oral route.

Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2

Obesity is widely recognized as cause of metabolic syndrome and cardiovascular disease. It is provoked by imbalance between the spending and consumption of energy associated with a chronic inflammatory condition due to excessive storage of fat tissue. Obese patients have an impaired inflammatory profile that contributes to the development of vascular complications, with fat tissue being partially responsible for controlling both processes: energy balance (through PPAR) and inflammatory condition (through inflammatory markers). White adipose tissue produces cytokines (IL-6, TNF-α, resistin, adiponectin, etc.) and participates in a broad spectrum of processes. Recently, glycine has been reported to have anti-inflammatory properties which reduce TNF-α and IL-6 levels and increase adiponectin in 3T3-L1 adipocytes and in fat tissue of obese mice. In this study, the possible regulatory role of glycine on some factors involved in storage and energy burning (PPAR-γ, PPAR-α, PPAR-δ and UCP-2) was analyzed in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Glycine clearly increased fat tissue PPAR-γ expression in lean but not in MSG/Ob mice. The PPAR-γ and PPAR-α liver expression was repressed in both groups of mice, while the expression of PPAR-δ decreased only in lean mice. Interestingly, glycine treatment also suppressed the expression of UCP-2, TNF-α and IL-6 in lean mice, and increased adiponectin and insulin serum levels. In conclusion, glycine regulates the production of inflammatory cytokines through PPAR-γ. These results provide clues on glycine signaling mechanisms as an anti-inflammatory agent that might be useful for treatment of metabolic and vascular complications associated to inflammation in obesity.

Hypoglycemic activity of root water decoction, sesquiterpenoids, and one polysaccharide fraction from Psacalium decompositum in mice.

The hypoglycemic activity of Psacalium decompositum (Asteraceae) was investigated in fasting healthy mice and alloxan-diabetic mice. The freeze-dried water decoction significantly reduced the blood glucose in normal mice (from 50.9 +/- 4.7 to 32.5 +/- 3.1 mg/dl) and in mild diabetic mice (from 208.5 +/- 13.0 to 52.3 +/- 7.0 mg/dl), 240 min after intraperitoneal administration (P < 0.005). This preparation also diminished fasting glycemia in severe diabetic mice, but the effects were minor (from 394.4 +/- 9.4 to 289.3 +/- 39.5 mg/dl). The main sesquiterpenoid constituents from P. decompositum roots, cacalol, cacalone and maturin, as well as the transformation product cacalol acetate, did not show a hypoglycemic effect on healthy mice. Nevertheless, two polysaccharide fractions (F1 and F3) obtained from the freeze-dried water extract significantly reduced the fasting glycemia in healthy mice. The best results were obtained with the F1 fraction.

Monosodium Glutamate Neonatal Intoxication Associated with Obesity in Adult Stage is Characterized by Chronic Inflammation and Increased mRNA Expression of Peroxisome Proliferator‐Activated Receptors in Mice

The monosodium glutamate (MSG) neonatal administration in mice provides a model of obesity with impaired glucose tolerance (IGT) and insulin resistance. However, the inflammatory profile of cytokines produced from fat tissue and its relationship to the metabolic dysfunction induced by MSG have not yet been revealed. The aim of this study was to establish the inflammatory profile attributed to MSG by measuring the expression of adipokines in visceral fat and serum of 19-week-old mice as well as the peroxisome proliferator-activated receptors alpha and gamma (PPARα and γ). Some metabolic and biochemical parameters were also quantified. The MSG increased mRNA expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNFα), resistin and leptin, but adiponectin did not exhibit any changes. In addition, impaired glucose tolerance, increased levels of insulin, resistin and leptin were observed in serum. Both PPARα and PPARγ were activated in MSG-induced obese mice, which might explain its inflammatory profile. However, liver transaminases were severely depressed, indicating that MSG may also induce liver injury, contributing to inflammation. The MSG neonatal neuro-intoxication in mice may thus provide a model of obesity and inflammation characterized by the dual activation of PPARα and PPARγ, which might offer new insights into the mechanism of inflammatory diabetes in obesity leading to steatohepatitis, as well as a suitable model to study the role of new therapeutic agents to prevent or reduce insulin resistance, the inflammatory state and liver steatosis.