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Journal RefereesInternational Journal of Diabetes in Developing Countries
Publications (18) View all
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Article: Oral Quercetin Supplementation Lowers Plasma sICAM-1 Concentrations in Female db/db Mice
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ABSTRACT: Background: Flavonoids are documented for their potential anti-adipogenic, anti-inflammatory and anti-diabetic effects. Quercetin, one of the most abundant flavonoids in edible plants, was investigated for these effects in a diabetic mouse model (db/db, leptin receptor mutation) exerting early relevant clinical signs of non-insulin dependent diabetes mellitus, such as hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypoadiponectinemia and obesity. Materials & Methods: Female db/db mice (n = 24) were fed a flavonoid-poor maintenance diet without (C) or with the addition of quercetin (0.3 g/kg diet, Q) or rosiglitazone (4 mg/kg diet, TZD). Food and water were freely available during the 4 week feeding period. Thereafter, blood samples (fasted) were analyzed for glucose, insulin, triacylglycerols, non-esterified fatty acids, cholesterol, adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1). Adiponectin mRNA levels were measured in adipose tissue. Furthermore, sICAM-1 release was investigated using tumor necrosis factor alpha stimulated EAhy926 cells. Results: Only TZD treatment reduced fasted plasma glucose, triacylglycerols and cholesterol and increased plasma adiponectin concentrations compared to groups C and Q. Adiponectin mRNA levels after quercetin treatment were not different from TZD-treatment or controls. Only quercetin treatment reduced sICAM-1 release in vitro and in vivo. Conclusions: Quercetin effectively reduced sICAM-1 release in the progressive diabetic state, revealing its anti-inflammatory potential in vivo.Pharmacology & Pharmacy 01/2013; 4(1):77. -
Article: Oral Bioavailability of Quercetin in Horses
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ABSTRACT: Quercetin, one of the most abundant flavonoids in plants, is discussed with respect to health-promoting effects like antioxidative and anti-inflammatory properties. Although most claims regarding biological effects of flavonoids are based on in vitro and ex vivo studies, the use of flavonoid-containing supplements in humans and companion animals has increased in recent years. Flavonoid-containing supplements are also offered for pet and livestock nutrition. However, any systemic effect of a substance within a living subject depends on its bioavailability. Therefore, the aim of the present study was to gain information on the oral bioavailability of quercetin in horses. Four Icelandic horses with a mean body weight (BW) of 315 ± 25 kg (mean ± standard error [SEM]) were fed a test meal (crimped oats 1 g/kg BW) with the addition of quercetin (20 mg/kg BW). Blood samples were collected directly from the jugular vein before and after ingestion of the test meal for 24 hours, and flavonoid content was analyzed by high-performance liquid chromatography. Quercetin was the main metabolite in plasma with intact flavonol structure after ?-glucuronidase/sulfatase treatment of blood samples. The area under the plasma concentration-time curve of quercetin accounted for 88% of total flavonols. Forty-seven percent of the quercetin detected in plasma after ingestion of the test meal was not conjugated. In addition to quercetin, the quercetin derivatives isorhamnetin (methylated) and kaempferol were detected in plasma. Although quercetin is orally bioavailable in horses, similar to other monogastric species, the plasma metabolite pattern differs from those found in species investigated previously (rat, dog, pig, and human)Journal of Equine Veterinary Science 11/2012; · 0.67 Impact Factor -
Article: Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin.
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ABSTRACT: The bioavailability of quercetin has been intensively investigated in monogastric species, but knowledge about its bioavailability in ruminants does not exist. Thus, the aim of the present study was to determine the bioavailability of quercetin in nonlactating cows equipped with indwelling catheters placed in one jugular vein after intraruminal and additionally after i.v. application, respectively. Quercetin was administered intraruminally in equimolar amounts, either in the aglycone form or as its glucorhamnoside rutin, each at 2 dosages [10 and 50 mg of quercetin/kg of body weight (BW)]. In a second trial, 0.8 mg of quercetin aglycone/kg of BW was applied i.v. Blood samples were drawn 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 h after intraruminal application and every 5 min (first hour), every 10 min(second hour), and at 3 and 6h after i.v. bolus application, respectively. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) in plasma samples were analyzed by HPLC with fluorescence detection. After intraruminal application of quercetin and rutin, respectively, quercetin and its methylated (isorhamnetin, tamarixetin) and dehydroxylated (kaempferol) derivatives were present in plasma mainly as conjugated forms, whereas free quercetin and its derivatives were scarcely detected. For rutin, the relative bioavailability of total flavonols (sum of conjugated and nonconjugated quercetin and its conjugated and nonconjugated derivatives after intake of 50 mg/kg of BW) was 767.3% compared with quercetin aglycone (100%). Absolute bioavailability of total flavonols was only 0.1 and 0.5% after quercetin aglycone and rutin applications, respectively. Our data demonstrate that bioavailability of quercetin from rutin is substantially higher compared with that from quercetin aglycone in cows after intraruminal (or oral) application, unlike in monogastric species.Journal of Dairy Science 09/2012; 95(9):5047-55. · 2.56 Impact Factor -
Article: Chronic quercetin feeding decreases plasma concentrations of salicylamide phase II metabolites in pigs following oral administration.
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ABSTRACT: We investigated acute effects and effects after chronic intake of the orally administered flavonol quercetin on pharmacokinetics of salicylamide metabolites (SAM) after oral administration of salicylamide in pigs. Salicylamide (8 mg/kg body weight) was orally administered to seven pigs either without or with quercetin (10 mg/kg body weight). Additionally, salicylamide was administered to five pigs that had received a diet supplemented with the flavonol for 1 week. Daily quercetin intake was 10 mg/kg in these animals. Co-ingestion of quercetin with the drug did not alter area under the concentration-time curve (AUC(0→∞)), time to achieve maximum plasma concentration (t(max)), mean residence time (MRT) or half-life (t(1/2)) of SAM. However, maximum plasma concentration (c(max)) of SAM was lower when quercetin was administered concomitantly. After quercetin pre-treatment for 1 week AUC(0→∞), t(1/2) and MRT of SAM were decreased, while other parameters investigated were not affected. Co-ingestions and dietary pre-treatment with quercetin influenced SAM metabolism after oral salicylamide intake. But effects seen after acute concomitant intake are rather explained by induced salicylamide excretion from the intestinal mucosa, whereas quercetin pre-treatment seemed to induce hepatic enzymes involved in phase-II metabolism and thereby enhanced elimination of SAM.Xenobiotica 12/2011; 42(5):477-82. · 1.79 Impact Factor -
Article: Synthesis and biological evaluation of L-valine-amidoximeesters as double prodrugs of amidines.
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ABSTRACT: In general, drugs containing amidines suffer from poor oral bioavailability and are often converted into amidoxime prodrugs to overcome low uptake from the gastrointestinal tract. The esterification of amidoximes with amino acids represents a newly developed double prodrug principle creating derivatives of amidines with both improved oral availability and water solubility. N-valoxybenzamidine (1) is a model compound for this principle, which has been transferred to the antiprotozoic drug pentamidine (8). Prodrug activation depends on esterases and mARC and is thus independent from activation by P450 enzymes. Therefore, drug-drug interactions or side effects will be minimized. The synthesis of these two compounds was established, and their biotransformation was studied in vitro and in vivo. Bioactivation of N-valoxybenzamidine (1) and N,N'-bis(valoxy)pentamidine (7) via hydrolysis and reduction has been demonstrated in vitro with porcine and human subcellular enzyme preparations and the mitochondrial Amidoxime Reducing Component (mARC). Moreover, activation of N-valoxybenzamidine (1) by porcine hepatocytes was studied. In vivo, the bioavailability in rats after oral application of N-valoxybenzamidine (1) was about 88%. Similarly, N,N'-bis(valoxy)pentamidine (7) showed oral bioavailability. Analysis of tissue samples revealed high concentrations of pentamidine (8) in liver and kidney.Bioorganic & medicinal chemistry 02/2011; 19(6):1907-14. · 2.82 Impact Factor
