Antihyperglycemic effect of casearia sylvestris leaves extract in streptozotocin induced diabetic rats

The antihyperglycaemic effect of Casearia sylvestris aqueous extract (CS) and its flavonoidic fraction using in vivo models in streptozotocin-induced diabetic rats was evaluated. CS (500 mg/kg) reduced blood glucose in rats three weeks after a single oral dose. The blood glucose significantly decreased in a test of tolerance to insulin. Phytochemical investigation on TLC, HPLC-DAD and NMR spectral analysis of extract and fractions confirmed the presence of flavonoids. These results direct the hypothesis that CS improves glucose metabolism by reducing insulin resistance, and it may be useful for the treatment of type 2 diabetes.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Antihyperglycemic effect of casearia sylvestris leaves extract in streptozotocin induced diabetic rats

The antihyperglycaemic effect of Casearia sylvestris aqueous extract (CS) and its flavonoidic fraction using in vivo models in streptozotocin-induced diabetic rats was evaluated. CS (500 mg/kg) reduced blood glucose in rats three weeks after a single oral dose. The blood glucose significantly decreased in a test of tolerance to insulin. Phytochemical investigation on TLC, HPLC-DAD and NMR spectral analysis of extract and fractions confirmed the presence of flavonoids. These results direct the hypothesis that CS improves glucose metabolism by reducing insulin resistance, and it may be useful for the treatment of type 2 diabetes.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Antihyperglycemic effect of casearia sylvestris leaves extract in streptozotocin induced diabetic rats

The antihyperglycaemic effect of Casearia sylvestris aqueous extract (CS) and its flavonoidic fraction using in vivo models in streptozotocin-induced diabetic rats was evaluated. CS (500 mg/kg) reduced blood glucose in rats three weeks after a single oral dose. The blood glucose significantly decreased in a test of tolerance to insulin. Phytochemical investigation on TLC, HPLC-DAD and NMR spectral analysis of extract and fractions confirmed the presence of flavonoids. These results direct the hypothesis that CS improves glucose metabolism by reducing insulin resistance, and it may be useful for the treatment of type 2 diabetes.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Satietogenic Protein from Tamarind Seeds Decreases Food Intake, Leptin Plasma and CCK-1r Gene Expression in Obese Wistar Rats

Objective: This study evaluated the effect of a protein, the isolated Trypsin Inhibitor (TTI) from Tamarindus indica L. seed, as a CCK secretagogue and its action upon food intake and leptin in obese Wistar rats. Methods: Three groups of obese rats were fed 10 days one of the following diets: Standard diet (Labina®) + water; High Glycemic Index and Load (HGLI) diet + water or HGLI diet + TTI. Lean animals were fed the standard diet for the 10 days. Food intake, zoometric measurements, plasma CCK, plasma leptin, relative mRNA expression of intestinal CCK-related genes, and expression of the ob gene in subcutaneous adipose tissue were assessed. Results: TTI decreased food intake but did not increase plasma CCK in obese animals. On the other hand, TTI treatment decreased CCK-1R gene expression in obese animals compared with the obese group with no treatment (p = 0.027). Obese animals treated with TTI presented lower plasma leptin than the non-treated obese animals. Conclusion: We suggest that TTI by decreasing plasma leptin may improve CCK action, regardless of its increase in plasma from obese rats, since food intake was lowest

Modulation of miR-26a-5p and miR-15b-5p exosomal expression associated with clopidogrel-induced hepatotoxicity in HepG2 cells

Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the present study, the expression of several exosomalmiRNAs (miR-26a-5p, miR-145-5p, miR-15b-5p, andmiR-4701-3p) and cell-derived mRNA targets (PLOD2, SENP5, EIF4G2, HMGA2, STRADB, and TLK1) were evaluated in HepG2 cells treated with clopidogrel (6.25, 12.5, 25, 50, and 100 mu M) for 24 and 48 h. Then, clopidogrel cytotoxicity was evaluated by analyzing DNA fragmentation and the cell cycle profile using flow cytometry. Differential expression of exosome-derived miRNAs and cell-derived mRNAs was analyzed by RT-qPCR. Exposure of HepG2 cells to high concentrations of clopidogrel (50 and 100 mu M) for 24 h caused significant DNA fragmentation (17.6 and 44.4%, respectively; p < 0.05) and 48 h (26.8 and 48.9%, respectively; p < 0.05), indicating cellular toxicity. Upregulation of miR-26a-5p and downregulation of miR-15b-5p was observed in cells exposed to 100 mu M clopidogrel for 24 and 48 h. The miR-26a-5p target mRNAs HMGA2, EIF4G2, STRADB, and SENP5 were downregulated in HepG2 cells following exposure to cytotoxic concentrations of clopidogrel (50 and 100 mu M) for 24 h, and HMGA2 levels remained low after 48 h of treatment. TLK1, a target of miR-15b-5p, was downregulated by 50 and 100 mu M clopidogrel at 24 h. In conclusion, our results suggest that exposure to high concentrations of clopidogrel modulates the expression of exosomal miR-26a-5p and miR-15b-5p and their target mRNAs in HepG2 cells. Dysregulation of these miRNAs maybe modulate the regulatory pathways involved in clopidogrel-induced liver injury8CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP448753/2014-6; 447120/2014-

Modulation of miR-26a-5p and miR-15b-5p Exosomal Expression Associated with Clopidogrel-Induced Hepatotoxicity in HepG2 Cells

Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the present study, the expression of several exosomal miRNAs (miR-26a-5p, miR-145-5p, miR-15b-5p, and miR-4701-3p) and cell-derived mRNA targets (PLOD2, SENP5, EIF4G2, HMGA2, STRADB, and TLK1) were evaluated in HepG2 cells treated with clopidogrel (6.25, 12.5, 25, 50, and 100 μM) for 24 and 48 h. Then, clopidogrel cytotoxicity was evaluated by analyzing DNA fragmentation and the cell cycle profile using flow cytometry. Differential expression of exosome-derived miRNAs and cell-derived mRNAs was analyzed by RT-qPCR. Exposure of HepG2 cells to high concentrations of clopidogrel (50 and 100 μM) for 24 h caused significant DNA fragmentation (17.6 and 44.4%, respectively; p &lt; 0.05) and 48 h (26.8 and 48.9%, respectively; p &lt; 0.05), indicating cellular toxicity. Upregulation of miR-26a-5p and downregulation of miR-15b-5p was observed in cells exposed to 100 μM clopidogrel for 24 and 48 h. The miR-26a-5p target mRNAs HMGA2, EIF4G2, STRADB, and SENP5 were downregulated in HepG2 cells following exposure to cytotoxic concentrations of clopidogrel (50 and 100 μM) for 24 h, and HMGA2 levels remained low after 48 h of treatment. TLK1, a target of miR-15b-5p, was downregulated by 50 and 100 μM clopidogrel at 24 h. In conclusion, our results suggest that exposure to high concentrations of clopidogrel modulates the expression of exosomal miR-26a-5p and miR-15b-5p and their target mRNAs in HepG2 cells. Dysregulation of these miRNAs maybe modulate the regulatory pathways involved in clopidogrel-induced liver injury

Anti-TNF-α Agent Tamarind Kunitz Trypsin Inhibitor Improves Lipid Profile of Wistar Rats Presenting Dyslipidemia and Diet-induced Obesity Regardless of PPAR-γ Induction

: The increasing prevalence of obesity and, consequently, chronic inflammation and its complications has increased the search for new treatment methods. The effect of the purified tamarind seed trypsin inhibitor (TTIp) on metabolic alterations in Wistar rats with obesity and dyslipidemia was evaluated. Three groups of animals with obesity and dyslipidemia were formed, consuming a high glycemic index and glycemic load (HGLI) diet, for 10 days: Obese/HGLI diet; Obese/standard diet; Obese/HGLI diet + TTIp (730 &#956;g/kg); and one eutrophic group of animals was fed a standard diet. Rats were evaluated daily for food intake and weight gain. On the 11th day, animals were anesthetized and sacrificed for blood and visceral adipose tissue collection. TTIp treated animals presented significantly lower food intake than the untreated group (p = 0.0065), TG (76.20 &#177; 18.73 mg/dL) and VLDL-C (15.24 &#177; 3.75 mg/dL). Plasma concentrations and TNF-&#945; mRNA expression in visceral adipose tissue also decreased in obese animals treated with TTIp (p &lt; 0.05 and p = 0.025, respectively) with a negative immunostaining. We conclude that TTIp presented anti-TNF-&#945; activity and an improved lipid profile of Wistar rats with dyslipidemia and obesity induced by a high glycemic index and load diet regardless of PPAR-&#947; induction