Detection of Baicalin Metabolites Baicalein and Oroxylin-A in Mouse Pancreas and Pancreatic Xenografts

Lu, Qing-Yi; Zhang, Zuo‐Feng; Moro, Aune; Chen, Monica C.; Harris, Diane M.; Eibl, Guido; Go, Vay-Liang W.

doi:10.1097/mpa.0b013e318232e130

Cited by 41 publications

(28 citation statements)

References 23 publications

(30 reference statements)

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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%

“…The mobile phase consisted of a binary gradient of 0.1% (v/v) ortho-phosphoric acid in water (eluent A) and acetonitrile (eluent B) as previously described [16,18]. Quercetin and metabolites were detected by UV absorbance at a wavelength of 258 nm and baicalin and metabolites were detected at 278 nm.…”

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%

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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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“…Six week-old male athymic nude mice (Nu/Nu; Charles River Laboratories, Wilmington, MA) were used for the subcutaneous (s.c.) xenograft model of pancreatic cancer (25). One week before tumor implantation, mice were randomly assigned to the following dietary groups (6 mice per group): control group , standard diet (AIN-76A, Dyets Inc); EA group , standard diet supplemented with ellagic acid (150 mg/kg diet; equivalent to a daily dose of 25 mg/kg body weight); EM group , standard diet supplemented with embelin (450 mg/kg diet equivalent to a daily dose of 75 mg/kg body weight), and EA+EM group , standard diet supplemented with ellagic acid and embelin (150 and 450 mg/kg diet, respectively).…”

Section: Methodsmentioning

confidence: 99%

Ellagic Acid and Embelin Affect Key Cellular Components of Pancreatic Adenocarcinoma, Cancer, and Stellate Cells

Edderkaoui

Lugea

Hui

et al. 2013

Nutrition and Cancer

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Ellagic acid is a polyphenolic phytochemical present in many fruits and nuts with anti-cancer properties demonstrated in experimental tumor studies. Embelin is a benzoquinone phytochemical isolated from the Japanese herb Ardisiae Japonicae and has been shown to induce apoptosis in cancer cells. We found that ellagic acid and embelin each dose-dependently increased apoptosis and inhibited proliferation in human pancreatic cancer cells, MIA PaCa-2 and HPAF-II cells, and in pancreatic stellate cells (PaSCs) which are progenitors of pancreatic cancer desmoplasia. In each of these cell types, combinations of ellagic acid and embelin at low micromolar concentrations (0.5–3 μM) induced synergistic increases in apoptosis and decreases in proliferation. Ellagic acid decreased NF-κB transcriptional activity, whereas embelin decreased STAT-3 phosphorylation and protein expression of its downstream target survivin, in cancer cells. In vivo dietary ellagic acid alone or in combination with embelin decreased tumor size and tumor cellularity in a subcutaneous (s.c.) xenograft mouse model of pancreatic cancer. These results show that ellagic acid and embelin interact with divergent intracellular signaling pathways resulting in augmentation of apoptosis and inhibition of proliferation at low micromolar concentrations for the key cellular components of pancreatic adenocarcinoma.

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“…We published a study measuring these levels in nude mice with subcutaneous xenograft tumors [50]. The mice ingested a diet contained 1% of Scutellaria baicalensis extract, 20% of which is the flavonoid baicalein, for 13 weeks.…”

Section: Bioavailabilitymentioning

confidence: 99%

Baicalein - An Intriguing Therapeutic Phytochemical in Pancreatic Cancer

Donald¹,

Hertzer²,

Eibl³

2012

CDT

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Despite advances in therapy for many of the most common cancers, advances which have led to corresponding improvements in survival rates, progress on the pancreatic cancer front have been slow and mortality rates remain startlingly high. New therapeutic strategies are needed. Phytochemicals are naturally occurring, plant-based substances that have garnered much interest in the research world for their anti-cancer properties, both as therapeutics and as components of the diet for chemoprevention. One particularly ubiquitous group of phytochemicals is the polyphenolic flavonoids. Baicalein, one such flavonoid, which has been widely studied in several malignancies, shows potent activity against pancreatic adenocarcinoma in both in vitro and in vivo studies. The mechanisms by which baicalein accomplishes this have recently been elucidated, and is through an induction of apoptosis in pancreatic cancer cells that are fiercely resistant to cell death. Compounds such as baicalein, offer promise in dietary chemoprevention, as chemotherapeutic adjuvants, or as targeted therapy.

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Detection of Baicalin Metabolites Baicalein and Oroxylin-A in Mouse Pancreas and Pancreatic Xenografts

Cited by 41 publications

References 23 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

Ellagic Acid and Embelin Affect Key Cellular Components of Pancreatic Adenocarcinoma, Cancer, and Stellate Cells

Baicalein - An Intriguing Therapeutic Phytochemical in Pancreatic Cancer

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