Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography

Peng, Huanjun; Cheng, Fu‐Chou; Huang, Yuanfei; Chen, C.F.; Tsai, Tsong-Ru

doi:10.1016/s0378-4347(98)00204-7

Cited by 104 publications

(60 citation statements)

References 17 publications

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“…In the present study, hesperidin metabolites recovered in plasma were identified as glucuronides of hesperetin, among which a low part was also sulphated. To our knowledge, the nature of the metabolites of flavanones in human plasma has never been described in the literature, but our results are in agreement with the findings of animal studies (Peng et al, 1998;Choudhury et al, 1999;Felgines et al, 2000). Besides, the presence of glucuronides of flavanones has been reported in human urine (Fuhr & Kummert, 1995;Ameer et al, 1996;Lee & Reidenberg, 1998).…”

Section: Discussionsupporting

confidence: 92%

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Manach¹,

Morand²,

et al. 2003

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Objective: Flavanones are polyphenols specific of citrus fruits, where they are present in high amounts. Although citrus fruits and juices are widely consumed in the world, little information has been published on flavanone bioavailability in humans. The aim of the present study was to determine the nature of the circulating metabolites, the plasma kinetics and the urinary excretion patterns of the flavanones, hesperidin and narirutin. Design: After an overnight fast, five healthy volunteers ingested 0.5 or 1 l of a commercial orange juice providing 444 mg=l hesperidin and 96.4 mg=l narirutin, together with a polyphenol-free breakfast. Blood was sampled at 10 different timepoints over a 24 h period. Urine was collected for 48 h, in five fractions. Results: Flavanones metabolites appeared in plasma 3 h after the juice ingestion, reached a peak between 5 and 7 h, then returned to baseline at 24 h. The peak plasma concentration of hesperetin was 0.46 AE 0.07 mmol=l and 1.28 AE 0.13 mmol=l after the 0.5 and 1 l intake, respectively. It was lower for naringenin: 0.20 AE 0.04 mmol=l after the 1 l dose. The circulating forms of hesperetin were glucuronides (87%) and sulphoglucuronides (13%). For both flavanones, the urinary excretion was nearly complete 24 h after the orange juice ingestion. The relative urinary excretion was similar for hesperetin and naringenin and did not depend on the dose: values ranged from 4.1 AE 1.2 to 7.9 AE 1.7% of the intake. Conclusions: In case of a moderate or high consumption of orange juice, flavanones may represent an important part of the pool of total polyphenols present in plasma.

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Section: Discussionsupporting

confidence: 92%

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Manach¹,

Morand²,

et al. 2003

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“…Peng et al, (1998) (121) demonstrated that the aglycone form of naringenin was detected in the cerebral cortex of rats following an IV bolus dose.…”

Section: Discussionmentioning

confidence: 99%

Phytoestrogens Modulate Breast Cancer Resistance Protein Expression and Function at the Blood-Cerebrospinal Fluid Barrier

Kaur

Badhan

2015

J Pharm Pharm Sci

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-PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS: Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS: A 24 hour cytotoxicity assay (0.001 µM-1000 µM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 µM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre-incubation with modulators alone, a 0.16-2.5 -fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-β-estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION: We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition.

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“…Their brain entry may also depend on their interactions with specific efflux transporters expressed in the BBB, such as P-glycoprotein [63] which appears to be responsible for the differences between naringenin and quercetin flux into the brain in situ [135]. In animals, flavanones have been found to enter the brain following their intravenous administration [79], whilst epigallocatechin gallate [115], epicatechin [3] and anthocyanins [26,116] Fig. 1 The structures of the main classes of flavonoids.…”

Section: Absorption Metabolism and Distribution Of Flavonoidsmentioning

confidence: 99%

The neuroprotective potential of flavonoids: a multiplicity of effects

et al. 2008

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Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

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Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography

Cited by 104 publications

References 17 publications

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Phytoestrogens Modulate Breast Cancer Resistance Protein Expression and Function at the Blood-Cerebrospinal Fluid Barrier

The neuroprotective potential of flavonoids: a multiplicity of effects

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