Young Jin Moon

Bio: Young Jin Moon is an academic researcher from State University of New York System. The author has contributed to research in topics: Biochanin A & Pharmacokinetics. The author has an hindex of 9, co-authored 9 publications receiving 1256 citations.

Quercetin pharmacokinetics in humans.

Abstract: The purpose of this study was to examine the pharmacokinetics of quercetin aglycone as well as its conjugated metabolites and to develop a population pharmacokinetic model for quercetin that incorporates enterohepatic recirculation. The stability of quercetin in different matrices at various temperatures and pH, and the quercetin content of six capsules of the herbal preparation Quercetin-500 Plus were determined by HPLC. Subjects received quercetin 500 mg three times daily and blood and urine samples were obtained. The concentration of quercetin aglycone and conjugated metabolites were assayed using a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis with WinNonlin. A population compartment model incorporating input from the gallbladder was developed to account for the enterohepatic recirculation observed with quercetin. The oral clearance (CL/F) was high (3.5 x 10(4)l/h) with an average terminal half-life of 3.5 h for quercetin. The plasma concentration versus time curves exhibited re-entry peaks. A one-compartment model that included enterohepatic recirculation best described the plasma data. This represents the first comprehensive evaluation of the pharmacokinetics and enterohepatic recirculation of quercetin in humans. Population pharmacokinetic models adapted for enterohepatic recirculation allowed an assessment of the magnitude and frequency of the enterohepatic recirculation process.

Pharmacokinetics and bioavailability of the isoflavone biochanin A in rats

Abstract: Biochanin A(BCA) is a dietary isoflavone present in legumes, most notably red clover, and in many herbal dietary supplements. BCA has been reported to have chemopreventive properties and is metabolized to the isoflavone genistein (GEN), BCA conjugates, and GEN conjugates. The metabolites may contribute to the chemopreventive effects of BCA. The absorption, metabolism, and disposition of BCA have not been determined in rats. Our objective was to evaluate the pharmacokinetics and metabolism of BCA in rats. Male Sprague-Dawley rats were administered BCA by intravenous injection (1 and 5 mg/kg), by intraperitoneal injection (5 and 50 mg/kg), and orally (5 and 50 mg/kg). Plasma and bile samples were enzymatically hydrolyzed in vitro to determine conjugate concentrations for BCA and GEN. Equilibrium dialysis was used to determine protein binding. The BCA and GEN concentrations in plasma, urine, and bile were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters of BCA were analyzed by noncompartmental analysis. Significant levels of BCA conjugates and GEN conjugates were detected in plasma and bile. Both BCA and GEN were found to have a high clearance and a large apparent volume of distribution; the bioavailability of both was poor (<4%). Reentry peaks were evident after oral administration of both BCA and GEN, suggesting enterohepatic cycling. The free fraction of BCA in rat plasma was 1.5%. A2-compartment model that included both linear and nonlinear clearance terms and enterohepatic recirculation best described the plasma data. This represents the first evaluation of the dose-dependent pharmacokinetics and metabolism of BCA in rats.

Pharmacokinetics and bioavailability of the bioflavonoid biochanin A: effects of quercetin and EGCG on biochanin A disposition in rats.

Abstract: Little is known regarding pharmacokinetic (PK) or pharmacodynamic interactions of flavonoids with each other: this is of significance since multiple flavonoids are present in the diet and in dietary supplements. Our objective was to determine the effect of quercetin and (-)-epigallocatechin-3-gallate (EGCG), major flavonoids present in the diet, on the PK and bioavailability of biochanin A, a flavonoid with chemopreventive properties. BCA was administered to rats intravenously (5 mg/kg) or orally (16.67 or 50 mg/kg) with or without concomitant EGCG and quercetin. In vitro studies with the human intestinal Caco-2 and human hepatic HepG2 cell lines were performed to evaluate the effects of quercetin and EGCG on the cellular metabolism of BCA, and studies with human breast cancer MCF-7 cells that overexpress P-glycoprotein or BCRP (MCF-7/ADR and MCF-7/MX100 cells, respectively) or MDCK cells that express MRP2 (MDCK-MRP2) were performed to evaluate the effects of cellular efflux. An HPLC assay was used to determine plasma, urine, and cellular concentrations of BCA and the conjugated metabolites of BCA (following enzymatic hydrolysis). The coadministration of quercetin and EGCG significantly increased the BCA area under the plasma concentration vs time curve (AUC) in rats, after both iv and oral administration of BCA. The AUC of total BCA (unchanged + conjugated) was also increased. The increases in BCA AUC reflected predominantly increased bioavailability; this was true even after iv administration due to an apparent increase in the enterohepatic cycling of BCA. Our findings demonstrate for the first time that the administration of multiple flavonoids results in increased flavonoid bioavailability, as well as a decrease in clearance, potentially due to increased enterohepatic cycling.

Biochanin A inhibits breast cancer tumor growth in a murine xenograft model

Abstract: Purpose Our objective was to determine the effect of the flavonoid biochanin A (BCA), administered alone or in combination with the flavonoids quercetin and epigallocatechin-3-gallate (EGCG), on the growth of human breast cancer MCF-7 cells in a murine xenograft animal model.

Quercetin, Inflammation and Immunity

Abstract: In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

Flavan-3-ols: nature, occurrence and biological activity.

Abstract: Representing the most common flavonoid consumed in the American diet, the flavan-3-ols and their polymeric condensation products, the proanthocyanidins, are regarded as functional ingredients in various beverages, whole and processed foods, herbal remedies and supplements. Their presence in food affects food quality parameters such as astringency, bitterness, sourness, sweetness, salivary viscosity, aroma, and color formation. The ability of flavan-3-ols to aid food functionality has also been established in terms of microbial stability, foamability, oxidative stability, and heat stability. While some foods only contain monomeric flavan-3-ols [(-)-epicatechin predominates] and dimeric proanthocyanidins, most foods contain oligomers of degree of polymerization values ranging from 1-10 or greater than 10. Flavan-3-ols have been reported to exhibit several health beneficial effects by acting as antioxidant, anticarcinogen, cardiopreventive, antimicrobial, anti-viral, and neuro-protective agents. This review summarizes the distribution and health effects of these compounds.

Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes

Abstract: Sex differences in pharmacokinetics and pharmacodynamics characterize many drugs and contribute to individual differences in drug efficacy and toxicity. Sex-based differences in drug metabolism are the primary cause of sex-dependent pharmacokinetics and reflect underlying sex differences in the expression of hepatic enzymes active in the metabolism of drugs, steroids, fatty acids and environmental chemicals, including cytochromes P450 (P450s), sulfotransferases, glutathione transferases, and UDP-glucuronosyltransferases. Studies in the rat and mouse liver models have identified more than 1000 genes whose expression is sex-dependent; together, these genes impart substantial sexual dimorphism to liver metabolic function and pathophysiology. Sex differences in drug metabolism and pharmacokinetics also occur in humans and are due in part to the female-predominant expression of CYP3A4, the most important P450 catalyst of drug metabolism in human liver. The sexually dimorphic expression of P450s and other liver-expressed genes is regulated by the temporal pattern of plasma growth hormone (GH) release by the pituitary gland, which shows significant sex differences. These differences are most pronounced in rats and mice, where plasma GH profiles are highly pulsatile (intermittent) in male animals versus more frequent (nearly continuous) in female animals. This review discusses key features of the cell signaling and molecular regulatory mechanisms by which these sex-dependent plasma GH patterns impart sex specificity to the liver. Moreover, the essential role proposed for the GH-activated transcription factor signal transducer and activator of transcription (STAT) 5b, and for hepatic nuclear factor (HNF) 4α, as mediators of the sex-dependent effects of GH on the liver, is evaluated. Together, these studies of the cellular, molecular, and gene regulatory mechanisms that underlie sex-based differences in liver gene expression have provided novel insights into the physiological regulation of both xenobiotic and endobiotic metabolism.