Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat

W.-L. Hung, W.-S. Chang, W.-C. Lu, G.-J. Wei, Y. Wang, C.-T. Ho, L.S. Hwang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. © 2017
Original languageEnglish
Pages (from-to)849-857
Number of pages9
JournalJournal of Food and Drug Analysis
Volume26
Issue number2
DOIs
Publication statusPublished - 2018
Externally publishedYes

Fingerprint

tissue distribution
Tissue Distribution
oral administration
Biological Availability
pharmacokinetics
bioavailability
excretion
Pharmacokinetics
rats
neuroprotective effect
fruit peels
citrus fruits
mandarins
Oral Administration
rectum
intravenous injection
cecum
colon
gastrointestinal system
small intestine

Keywords

  • Excretion
  • Oral bioavailability
  • Pharmacokinetics
  • Tangeretin
  • Tissue distribution
  • drug metabolite
  • tangeretin
  • animal experiment
  • animal tissue
  • area under the curve
  • Article
  • cecum
  • colon
  • controlled study
  • drug absorption
  • drug bioavailability
  • drug elimination
  • drug excretion
  • drug half life
  • feces
  • gastrointestinal tract
  • heart
  • in vivo study
  • kidney
  • limit of detection
  • limit of quantitation
  • liquid chromatography-mass spectrometry
  • liver
  • lung
  • male
  • maximum concentration
  • nonhuman
  • rat
  • rectum
  • small intestine
  • spleen
  • stomach
  • time to maximum plasma concentration
  • tissue distribution
  • urinary excretion

Cite this

Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. / Hung, W.-L.; Chang, W.-S.; Lu, W.-C.; Wei, G.-J.; Wang, Y.; Ho, C.-T.; Hwang, L.S.

In: Journal of Food and Drug Analysis, Vol. 26, No. 2, 2018, p. 849-857.

Research output: Contribution to journalArticle

Hung, W.-L. ; Chang, W.-S. ; Lu, W.-C. ; Wei, G.-J. ; Wang, Y. ; Ho, C.-T. ; Hwang, L.S. / Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. In: Journal of Food and Drug Analysis. 2018 ; Vol. 26, No. 2. pp. 849-857.
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title = "Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat",
abstract = "Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11{\%}. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026{\%} and 7.54{\%}, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. {\circledC} 2017",
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author = "W.-L. Hung and W.-S. Chang and W.-C. Lu and G.-J. Wei and Y. Wang and C.-T. Ho and L.S. Hwang",
note = "Export Date: 19 September 2018 CODEN: YSFEE 通訊地址: Hwang, L.S.; Graduate Institute of Food Science and Technology, National Taiwan University, No. 1, Section 4, Roosevelt Rd., Taiwan; 電子郵件: lshwang@ntu.edu.tw 化學物質/CAS: tangeretin, 481-53-8 參考文獻: Pan, M.H., Lai, C.S., Wu, J.C., Ho, C.T., Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds (2011) Mol Nutr Food Res, 55, pp. 32-45; Kim, H.P., Son, K.H., Chang, H.W., Kang, S.S., Anti-inflammatory plant flavonoids and cellular action mechanisms (2004) J Pharmacol Sci, 96, pp. 229-245; Vauzour, D., Vafeiadou, K., Rodriguez-Mateos, A., Rendeiro, C., Spencer, J.P., The neuroprotective potential of flavonoids: a multiplicity of effects (2008) Genes Nutr, 3, pp. 115-126; Li, S., Pan, M.H., Lo, C.-Y., Tan, D., Wang, Y., Shahidi, F., Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones (2009) J Funct Foods, 1, pp. 2-12; Li, S., Wang, H., Guo, L., Zhao, H., Ho, C.T., Chemistry and bioactivity of nobiletin and its metabolites (2014) J Funct Foods, 6, pp. 2-10; Lai, C.S., Wu, J.C., Ho, C.T., Pan, M.H., Disease chemopreventive effects and molecular mechanisms of hydroxylated polymethoxyflavones (2015) Biofactors, 41, pp. 301-313; Lou, S.N., Ho, C.T., Phenolic compounds and biological activities of small-size citrus: Kumquat and calamondin (2017) J Food Drug Anal, 25, pp. 162-175; Nogata, Y., Sakamoto, K., Shiratsuchi, H., Ishii, T., Yano, M., Ohta, H., Flavonoid composition of fruit tissues of citrus species (2006) Biosci Biotech Biochem, 70, pp. 178-192; Feng, X., Zhang, Q., Cong, P., Zhu, Z., Simultaneous determination of flavonoids in different citrus fruit juices and beverages by high-performance liquid chromatography and analysis of their chromatographic profiles by chemometrics (2012) Anal Methods, 4, pp. 3748-3753; Onda, K., Horike, N., Suzuki, T., Hirano, T., Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine adipocytes (2013) Phytother Res, 27, pp. 312-316; Lakshmi, A., Subramanian, S., Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats (2014) Biochimie, 99, pp. 96-109; Chen, K.H., Weng, M.S., Lin, J.K., Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells (2007) Biochem Pharmacol, 73, pp. 215-227; Sundaram, R., Shanthi, P., Sachdanandam, P., Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats (2014) Phytomedicine, 21, pp. 793-799; Kawaii, S., Tomono, Y., Katase, E., Ogawa, K., Yano, M., Antiproliferative activity of flavonoids on several cancer cell lines (1999) Biosci Biotech Biochem, 63, pp. 896-899; Lee, Y.Y., Lee, E.J., Park, J.S., Jang, S.E., Kim, D.H., Kim, H.S., Anti-inflammatory and antioxidant mechanism of tangeretin in activated microglia (2016) J Neuroimmune Pharm, 11, pp. 294-305; Lei, L., Li, Y.M., Wang, X., Liu, Y., Ma, K.Y., Wang, L., Plasma triacylglycerol-lowering activity of citrus polymethoxylated flavones is mediated by modulating the genes involved in lipid metabolism in hamsters (2016) Eur J Lipid Sci Tech, 118, pp. 147-156; Ma, L.L., Wang, D.W., Yu, X.D., Zhou, Y.L., Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells (2016) Biomed Pharmacother, 81, pp. 491-496; Kurowska, E.M., Manthey, J.A., Casaschi, A., Theriault, A.G., Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin (2004) Lipids, 39, pp. 143-151; Shu, Z., Yang, B., Zhao, H., Xu, B., Jiao, W., Wang, Q., Tangeretin exerts anti-neuroinflammatory effects via NF-kappaB modulation in lipopolysaccharide-stimulated microglial cells (2014) Int Immunopharmacol, 19, pp. 275-282; Kandaswami, C., Perkins, E., Soloniuk, D.S., Drzewiecki, G., Middleton, E., Jr., Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro (1991) Cancer Lett, 56, pp. 147-152; Hu, Y.-T., Ting, Y., Hu, J.Y., Hsieh, S.C., Techniques and methods to study functional characteristics of emulsion systems (2017) J Food Drug Anal, 25, pp. 16-26; He, X., Hwang, H.M., Nanotechnology in food science: functionality, applicability, and safety assessment (2016) J Food Drug Anal, 24, pp. 671-681; Manthey, J.A., Cesar, T.B., Jackson, E., Mertens-Talcott, S., Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry (2011) J Agric Food Chem, 59, pp. 145-151; Nielsen, S.E., Breinholt, V., Cornett, C., Dragsted, L.O., Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus (2000) Food Chem Toxicol, 38, pp. 739-746; Wei, G.J., Hwang, L.S., Tsai, C.L., Absolute bioavailability, pharmacokinetics and excretion of 5,7,3′,4′-tetramethoxyflavone in rats (2014) J Funct Foods, 7, pp. 136-141; Causon, R., Validation of chromatographic methods in biomedical analysis. Viewpoint and discussion (1997) J Chromatogr B, 689, pp. 175-180; Kumar, A., Devaraj, V.C., Giri, K.C., Giri, S., Rajagopal, S., Mullangi, R., Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of nobiletin in rat plasma: application to a pharmacokinetic study (2012) Biomed Chromatogr, 26, pp. 1464-1471; Li, T., Yan, Z., Zhou, C., Sun, J., Jiang, C., Yang, X., Simultaneous quantification of paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin from Si-Ni-San extract in rat plasma and tissues by liquid chromatography-tandem mass spectrometry (2013) Biomed Chromatogr, 27, pp. 1041-1053; Wen, X., Walle, T., Methylated flavonoids have greatly improved intestinal absorption and metabolic stability (2006) Drug Metab Dispos, 34, pp. 1786-1792; Mekjaruskul, C., Jay, M., Sripanidkulchai, B., Pharmacokinetics, bioavailability, tissue distribution, excretion, and metabolite identification of methoxyflavones in Kaempferia parviflora extract in rats (2012) Drug Metab Dispos, 40, pp. 2342-2353; Walle, T., Ta, N., Kawamori, T., Wen, X., Tsuji, P.A., Walle, U.K., Cancer chemopreventive properties of orally bioavailable flavonoids–methylated versus unmethylated flavones (2007) Biochem Pharmacol, 73, pp. 1288-1296; Datla, K.P., Christidou, M., Widmer, W.W., Rooprai, H.K., Dexter, D.T., Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease (2001) Neuroreport, 12, pp. 3871-3875; Murakami, A., Koshimizu, K., Ohigashi, H., Kuwahara, S., Kuki, W., Takahashi, Y., Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin (2002) Biofactors, 16, pp. 73-82; Bei, D., An, G., Pharmacokinetics and tissue distribution of 5,7-dimethoxyflavone in mice following single dose oral administration (2016) J Pharm Biomed Anal, 119, pp. 65-70; Wen, X., Walle, T., Methylation protects dietary flavonoids from rapid hepatic metabolism (2006) Xenobiotica, 36, pp. 387-397; Nielsen, S.E., Breinholt, V., Justesen, U., Cornett, C., Dragsted, L.O., In vitro biotransformation of flavonoids by rat liver microsomes (1998) Xenobiotica, 28, pp. 389-401; Burapan, S., Kim, M., Han, J., Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp. MRG-PMF1 (2017) J Agric Food Chem, 65, pp. 1620-1629; Kim, M., Kim, N., Han, J., Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1 (2014) J Agric Food Chem, 62, pp. 12377-12383",
year = "2018",
doi = "10.1016/j.jfda.2017.08.003",
language = "English",
volume = "26",
pages = "849--857",
journal = "Journal of Food and Drug Analysis",
issn = "1021-9498",
publisher = "Elsevier Taiwan LLC",
number = "2",

}

TY - JOUR

T1 - Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat

AU - Hung, W.-L.

AU - Chang, W.-S.

AU - Lu, W.-C.

AU - Wei, G.-J.

AU - Wang, Y.

AU - Ho, C.-T.

AU - Hwang, L.S.

N1 - Export Date: 19 September 2018 CODEN: YSFEE 通訊地址: Hwang, L.S.; Graduate Institute of Food Science and Technology, National Taiwan University, No. 1, Section 4, Roosevelt Rd., Taiwan; 電子郵件: lshwang@ntu.edu.tw 化學物質/CAS: tangeretin, 481-53-8 參考文獻: Pan, M.H., Lai, C.S., Wu, J.C., Ho, C.T., Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds (2011) Mol Nutr Food Res, 55, pp. 32-45; Kim, H.P., Son, K.H., Chang, H.W., Kang, S.S., Anti-inflammatory plant flavonoids and cellular action mechanisms (2004) J Pharmacol Sci, 96, pp. 229-245; Vauzour, D., Vafeiadou, K., Rodriguez-Mateos, A., Rendeiro, C., Spencer, J.P., The neuroprotective potential of flavonoids: a multiplicity of effects (2008) Genes Nutr, 3, pp. 115-126; Li, S., Pan, M.H., Lo, C.-Y., Tan, D., Wang, Y., Shahidi, F., Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones (2009) J Funct Foods, 1, pp. 2-12; Li, S., Wang, H., Guo, L., Zhao, H., Ho, C.T., Chemistry and bioactivity of nobiletin and its metabolites (2014) J Funct Foods, 6, pp. 2-10; Lai, C.S., Wu, J.C., Ho, C.T., Pan, M.H., Disease chemopreventive effects and molecular mechanisms of hydroxylated polymethoxyflavones (2015) Biofactors, 41, pp. 301-313; Lou, S.N., Ho, C.T., Phenolic compounds and biological activities of small-size citrus: Kumquat and calamondin (2017) J Food Drug Anal, 25, pp. 162-175; Nogata, Y., Sakamoto, K., Shiratsuchi, H., Ishii, T., Yano, M., Ohta, H., Flavonoid composition of fruit tissues of citrus species (2006) Biosci Biotech Biochem, 70, pp. 178-192; Feng, X., Zhang, Q., Cong, P., Zhu, Z., Simultaneous determination of flavonoids in different citrus fruit juices and beverages by high-performance liquid chromatography and analysis of their chromatographic profiles by chemometrics (2012) Anal Methods, 4, pp. 3748-3753; Onda, K., Horike, N., Suzuki, T., Hirano, T., Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine adipocytes (2013) Phytother Res, 27, pp. 312-316; Lakshmi, A., Subramanian, S., Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats (2014) Biochimie, 99, pp. 96-109; Chen, K.H., Weng, M.S., Lin, J.K., Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells (2007) Biochem Pharmacol, 73, pp. 215-227; Sundaram, R., Shanthi, P., Sachdanandam, P., Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats (2014) Phytomedicine, 21, pp. 793-799; Kawaii, S., Tomono, Y., Katase, E., Ogawa, K., Yano, M., Antiproliferative activity of flavonoids on several cancer cell lines (1999) Biosci Biotech Biochem, 63, pp. 896-899; Lee, Y.Y., Lee, E.J., Park, J.S., Jang, S.E., Kim, D.H., Kim, H.S., Anti-inflammatory and antioxidant mechanism of tangeretin in activated microglia (2016) J Neuroimmune Pharm, 11, pp. 294-305; Lei, L., Li, Y.M., Wang, X., Liu, Y., Ma, K.Y., Wang, L., Plasma triacylglycerol-lowering activity of citrus polymethoxylated flavones is mediated by modulating the genes involved in lipid metabolism in hamsters (2016) Eur J Lipid Sci Tech, 118, pp. 147-156; Ma, L.L., Wang, D.W., Yu, X.D., Zhou, Y.L., Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells (2016) Biomed Pharmacother, 81, pp. 491-496; Kurowska, E.M., Manthey, J.A., Casaschi, A., Theriault, A.G., Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin (2004) Lipids, 39, pp. 143-151; Shu, Z., Yang, B., Zhao, H., Xu, B., Jiao, W., Wang, Q., Tangeretin exerts anti-neuroinflammatory effects via NF-kappaB modulation in lipopolysaccharide-stimulated microglial cells (2014) Int Immunopharmacol, 19, pp. 275-282; Kandaswami, C., Perkins, E., Soloniuk, D.S., Drzewiecki, G., Middleton, E., Jr., Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro (1991) Cancer Lett, 56, pp. 147-152; Hu, Y.-T., Ting, Y., Hu, J.Y., Hsieh, S.C., Techniques and methods to study functional characteristics of emulsion systems (2017) J Food Drug Anal, 25, pp. 16-26; He, X., Hwang, H.M., Nanotechnology in food science: functionality, applicability, and safety assessment (2016) J Food Drug Anal, 24, pp. 671-681; Manthey, J.A., Cesar, T.B., Jackson, E., Mertens-Talcott, S., Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry (2011) J Agric Food Chem, 59, pp. 145-151; Nielsen, S.E., Breinholt, V., Cornett, C., Dragsted, L.O., Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus (2000) Food Chem Toxicol, 38, pp. 739-746; Wei, G.J., Hwang, L.S., Tsai, C.L., Absolute bioavailability, pharmacokinetics and excretion of 5,7,3′,4′-tetramethoxyflavone in rats (2014) J Funct Foods, 7, pp. 136-141; Causon, R., Validation of chromatographic methods in biomedical analysis. Viewpoint and discussion (1997) J Chromatogr B, 689, pp. 175-180; Kumar, A., Devaraj, V.C., Giri, K.C., Giri, S., Rajagopal, S., Mullangi, R., Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of nobiletin in rat plasma: application to a pharmacokinetic study (2012) Biomed Chromatogr, 26, pp. 1464-1471; Li, T., Yan, Z., Zhou, C., Sun, J., Jiang, C., Yang, X., Simultaneous quantification of paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin from Si-Ni-San extract in rat plasma and tissues by liquid chromatography-tandem mass spectrometry (2013) Biomed Chromatogr, 27, pp. 1041-1053; Wen, X., Walle, T., Methylated flavonoids have greatly improved intestinal absorption and metabolic stability (2006) Drug Metab Dispos, 34, pp. 1786-1792; Mekjaruskul, C., Jay, M., Sripanidkulchai, B., Pharmacokinetics, bioavailability, tissue distribution, excretion, and metabolite identification of methoxyflavones in Kaempferia parviflora extract in rats (2012) Drug Metab Dispos, 40, pp. 2342-2353; Walle, T., Ta, N., Kawamori, T., Wen, X., Tsuji, P.A., Walle, U.K., Cancer chemopreventive properties of orally bioavailable flavonoids–methylated versus unmethylated flavones (2007) Biochem Pharmacol, 73, pp. 1288-1296; Datla, K.P., Christidou, M., Widmer, W.W., Rooprai, H.K., Dexter, D.T., Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease (2001) Neuroreport, 12, pp. 3871-3875; Murakami, A., Koshimizu, K., Ohigashi, H., Kuwahara, S., Kuki, W., Takahashi, Y., Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin (2002) Biofactors, 16, pp. 73-82; Bei, D., An, G., Pharmacokinetics and tissue distribution of 5,7-dimethoxyflavone in mice following single dose oral administration (2016) J Pharm Biomed Anal, 119, pp. 65-70; Wen, X., Walle, T., Methylation protects dietary flavonoids from rapid hepatic metabolism (2006) Xenobiotica, 36, pp. 387-397; Nielsen, S.E., Breinholt, V., Justesen, U., Cornett, C., Dragsted, L.O., In vitro biotransformation of flavonoids by rat liver microsomes (1998) Xenobiotica, 28, pp. 389-401; Burapan, S., Kim, M., Han, J., Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp. MRG-PMF1 (2017) J Agric Food Chem, 65, pp. 1620-1629; Kim, M., Kim, N., Han, J., Metabolism of Kaempferia parviflora polymethoxyflavones by human intestinal bacterium Bautia sp. MRG-PMF1 (2014) J Agric Food Chem, 62, pp. 12377-12383

PY - 2018

Y1 - 2018

N2 - Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. © 2017

AB - Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. © 2017

KW - Excretion

KW - Oral bioavailability

KW - Pharmacokinetics

KW - Tangeretin

KW - Tissue distribution

KW - drug metabolite

KW - tangeretin

KW - animal experiment

KW - animal tissue

KW - area under the curve

KW - Article

KW - cecum

KW - colon

KW - controlled study

KW - drug absorption

KW - drug bioavailability

KW - drug elimination

KW - drug excretion

KW - drug half life

KW - feces

KW - gastrointestinal tract

KW - heart

KW - in vivo study

KW - kidney

KW - limit of detection

KW - limit of quantitation

KW - liquid chromatography-mass spectrometry

KW - liver

KW - lung

KW - male

KW - maximum concentration

KW - nonhuman

KW - rat

KW - rectum

KW - small intestine

KW - spleen

KW - stomach

KW - time to maximum plasma concentration

KW - tissue distribution

KW - urinary excretion

U2 - 10.1016/j.jfda.2017.08.003

DO - 10.1016/j.jfda.2017.08.003

M3 - Article

VL - 26

SP - 849

EP - 857

JO - Journal of Food and Drug Analysis

JF - Journal of Food and Drug Analysis

SN - 1021-9498

IS - 2

ER -