Quercetin Aglycone Is Bioavailable in Murine Pancreas and Pancreatic Xenografts

Zhang, Zuo‐Feng; Angst, Eliane; Park, Jenny L.; Moro, Aune; Dawson, David W.; Reber, Howard A.; Eibl, Guido; Hines, Oscar J.; Go, Vay-Liang W.; Lu, Qing-Yi

doi:10.1021/jf101192k

Cited by 30 publications

(32 citation statements)

References 37 publications

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“…1) and their metabolites in mouse tissues and human tumor xenografts, we found a large percentage of aglycones present in various organ tissues and tumors but a limited amount present in plasma [15,16]. These data are consistent with literature on the flavonoid aglycones found in tissues from humans, pigs and rats administered orally with quercetin or baicalin diet [13,17].…”

Section: Introductionsupporting

confidence: 87%

“…The pancreatic xenograft mouse model fed with standard diet (AIN-93G, Dyets, Bethlehem, PA, USA) and standard diet supplemented with 1% or 5% quercetin, or 1% Scutellaria baicalensis Georgi (SB) extract containing 20.6% (wt/wt) baicalin has been reported previously [18,19]. In both studies, orthotopic tumor xenografts in nude mice (Charles River Laboratories, San Diego, CA, USA) were established by implantation of a small piece of subcutaneously grown xenografts of human pancreatic cancer cells (MiaPaCa-2).…”

Section: Methodsmentioning

confidence: 99%

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Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue β-glucuronidase

Zhang

Eibl

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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Flavonoid glucuronides are the main circulating metabolites of flavonoids in humans and animals. There has been a growing interest in the biological function of glucuronides. In order to differentiate biological activity and to assess efficacy it is essential to accurately determine the levels of flavonoid aglycone and metabolic conjugate in vivo. Many organs and body fluids of humans and animals exhibit β-glucuronidase against flavonoid glucuronides. Studies have shown that β-glucuronidase within the tissues hydrolyzes glucuronides to their aglycones during the tissue extraction, leading to artificially higher reported tissue levels of aglycone than actual in vivo concentrations. The aims of this study were to estimate the extent by which the aglycones were overestimated and to investigate the use of saccharo-1,4-lactone, a β-glucuronidase inhibitor, to block the ex vivo hydrolysis of flavonoid glucuronides. Our data demonstrate that in mouse liver tissues and human tumor xenografts levels of quercetin and methylated quercetin aglycones could be over-estimated by 7 fold. The inhibition of deconjugation of quercetin and baicalein glucuronides by saccharo-1,4-lactone is dose-dependent. The amount of saccharo-1,4-lactone used to produce optimal inhibition of the enzyme activity is in the range of 15 – 24 μmol per gram of liver tissue. The use of β-glucuronidase inhibitor blocks the ex vivo deconjugation resulting in an accurate estimation of tissue levels of aglycone and conjugate. Our study described here can be extended to other animal models and human studies with different types of substrates of β-glucuronidase.

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Section: Introductionsupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue β-glucuronidase

Zhang

Eibl

et al. 2014

Journal of Pharmaceutical and Biomedical Analysis

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“…The extraction of quercetin and its metabolite isorhamnetin was carried out according to the published method with slight modification [21]. Briefly, approximately 200 mg of mouse liver was weighed, cut and homogenized in 200 μL water containing 2% ascorbic acid using Precellys homogenizer.…”

Section: Methodsmentioning

confidence: 99%

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

et al. 2016

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The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.

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“…4A. The protocol of the study is based on the method of Zhang et al, (2010) [43]. The mice in the treatment group were administered 10 mg capsaicin per kg body weight (dissolved in ethanol) by oral gavage.…”

Section: Bioavailability and Metabolism Of Capsaicinoids In Vivomentioning

confidence: 99%

Bioavailability of capsaicin and its implications for drug delivery

Rollyson

Stover

Brown

et al. 2014

Journal of Controlled Release

210

160

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The dietary compound capsaicin is responsible for the “hot and spicy” taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease.

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Quercetin Aglycone Is Bioavailable in Murine Pancreas and Pancreatic Xenografts

Cited by 30 publications

References 37 publications

Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue β-glucuronidase

Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue β-glucuronidase

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

Bioavailability of capsaicin and its implications for drug delivery

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