The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability

References

• Ali F. Rahul, F. Naz, S. Jyoti, and Y. H. Siddique. 2017. Health functionality of apigenin: A review. International Journal of Food Properties 20 (6):1197–238. doi: 10.1080/10942912.2016.1207188.
   Web of Science ®Google Scholar
• Alrushaid, S., N. Davies, S. Martinez, and C. Sayre. 2017. Stereospecific pharmacokinetic characterization of liquiritigenin in the rat. Research in Pharmaceutical Sciences 12 (3):176. doi: 10.4103/1735-5362.207197.
   PubMed Web of Science ®Google Scholar
• Barberis, A., A. Garbetta, A. Cardinali, G. Bazzu, I. D'Antuono, G. Rocchitta, A. Fadda, V. Linsalata, G. D'Hallewin, P. A. Serra, et al. 2017. Real-time monitoring of glucose and phenols intestinal absorption through an integrated Caco-2TC7cells/biosensors telemetric device: Hypoglycemic effect of fruit phytochemicals. Biosensors & Bioelectronics 88:159–66. doi: 10.1016/j.bios.2016.08.007.
   PubMed Web of Science ®Google Scholar
• Bernatova, I. 2018. Biological activities of (-)-epicatechin and (-)-epicatechin-containing foods: Focus on cardiovascular and neuropsychological health. Biotechnology Advances 36 (3):666–81. doi: 10.1016/j.biotechadv.2018.01.009.
   PubMed Web of Science ®Google Scholar
• Billat, P.-A., E. Roger, S. Faure, and F. Lagarce. 2017. Models for drug absorption from the small intestine: Where are we and where are we going? Drug Discovery Today 22 (5):761–75. doi: 10.1016/j.drudis.2017.01.007.
   PubMed Web of Science ®Google Scholar
• Bittner, K., T. Kemme, K. Peters, S. Kersten, S. Dänicke, and H. U. Humpf. 2014. Systemic absorption and metabolism of dietary procyanidin B4 in pigs. Molecular Nutrition & Food Research 58 (12):2261–73. doi: 10.1002/mnfr.201400435.
   PubMed Web of Science ®Google Scholar
• Buqui, G. A., S. K. Sy, M. Merino-Sanjuán, D. R. Gouvea, S. L. Nixdorf, E. Kimura, H. Derendorf, N. P. Lopes, and A. Diniz. 2015. Characterization of intestinal absorption of C-glycoside flavonoid vicenin-2 from Lychnophora ericoides leafs in rats by nonlinear mixed effects modeling. Revista Brasileira de Farmacognosia 25 (3):212–8. doi: 10.1016/j.bjp.2015.04.001.
   Google Scholar
• Caifu, X., G. Jianming, Q. Dawei, D. Jinao, and S. Yan. 2011. Absorption of flavonoids from Abelmoschus manihot extract by in situ intestinal perfusion. Acta Pharmaceutica Sinica 46 (04):454–9.
   PubMedGoogle Scholar
• Cao, F., J.-X. Guo, Q.-N. Ping, and Z.-G. Liao. 2006. Prodrugs of scutellarin: Ethyl, benzyl and N, N-diethylglycolamide ester synthesis, physicochemical properties, intestinal metabolism and oral bioavailability in the rats. European Journal of Pharmaceutical Sciences 29 (5):385–93. doi: 10.1016/j.ejps.2006.07.007.
   PubMed Web of Science ®Google Scholar
• Chen, C., Z. Wang, Z. Zhang, X. Liu, S. S. Kang, Y. Zhang, and K. Ye. 2018. The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 115 (3):578–83. doi: 10.1073/pnas.1718683115.
   PubMed Web of Science ®Google Scholar
• Chen, L., H. Cao, and J. Xiao. 2018. Polyphenols: Absorption, bioavailability, and metabolomics. In. Polyphenols: Properties, recovery, and applications, eds L. S. Taylor, 45–67. Washington: Elsevier. doi: 10.1016/B978-0-12-813572-3.00002-6.
   Google Scholar
• Chen, T., Y. Li, C. Li, X. Yi, R. Wang, S. M.-Y. Lee, and Y. Zheng. 2017. Pluronic P85/F68 micelles of baicalein could interfere with mitochondria to overcome MRP2-mediated efflux and offer improved anti-Parkinsonian activity. Molecular Pharmaceutics 14 (10):3331–42. doi: 10.1021/acs.molpharmaceut.7b00374.
   PubMed Web of Science ®Google Scholar
• Chuanlian, R., D. Junguo, J. Wenyuan, and L. Qing. 2012. Advances in research on pharmacokinetics of puerarin. Pharmacology and Clinics of Chinese Materia Medica 28 (01):190–4. doi: 10.13412/j.cnki.zyyl.2012.01.061.
   Google Scholar
• Copmans, D., A. M. Orellana-Paucar, G. Steurs, Y. Zhang, A. Ny, K. Foubert, V. Exarchou, A. Siekierska, Y. Kim, W. De Borggraeve, et al. 2018. Methylated flavonoids as anti-seizure agents: Naringenin 4',7-dimethyl ether attenuates epileptic seizures in zebrafish and mouse models . Neurochemistry International 112:124–33. doi: 10.1016/j.neuint.2017.11.011.
   PubMed Web of Science ®Google Scholar
• Costa, L. G., J. M. Garrick, P. J. Roquè, and C. Pellacani. 2016. Mechanisms of neuroprotection by quercetin: Counteracting oxidative stress and more. Oxidative Medicine and Cellular Longevity 2016:2986796. doi: 10.1155/2016/2986796.
   PubMed Web of Science ®Google Scholar
• Čvorović, J., L. Ziberna, S. Fornasaro, F. Tramer, and S. Passamonti. 2018. Bioavailability of flavonoids: The role of cell membrane transporters. In Polyphenols: Mechanisms of action in human health and disease, eds R. R. Watson, V. R. Preedy and S. Zibadi, 295–320. Cambridge: Elsevier. doi: 10.1016/B978-0-12-813006-3.00022-2.
   Google Scholar
• Dangles, O., C. Dufour, C. Manach, C. Morand, and C. Remesy. 2001. Binding of flavonoids to plasma proteins. In Methods in enzymology, eds L. Packer, vol. 335, 319–33. Cambridge: Elsevier. doi: 10.1016/S0076-6879(01)35254-0.
   Google Scholar
• Davatgaran-Taghipour, Y., S. Masoomzadeh, M. H. Farzaei, R. Bahramsoltani, Z. Karimi-Soureh, R. Rahimi, and M. Abdollahi. 2017. Polyphenol nanoformulations for cancer therapy: Experimental evidence and clinical perspective. International Journal of Nanomedicine 12:2689–702. doi: 10.2147/IJN.S131973.
   PubMed Web of Science ®Google Scholar
• Day, A. J., F. J. Cañada, J. C. Díaz, P. A. Kroon, R. Mclauchlan, C. B. Faulds, G. W. Plumb, M. R. Morgan, and G. Williamson. 2000. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Letters 468 (2-3):166–70. doi: 10.1016/S0014-5793(00)01211-4.
   PubMed Web of Science ®Google Scholar
• Devadoss, D., M. Ramar, and A. Chinnasamy. 2018. Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status. Archives of Pharmacal Research 41 (3):265–75. doi: 10.1007/s12272-014-0330-8.
   PubMed Web of Science ®Google Scholar
• Dhaneshwar, S., and N. V. Bhilare. 2020. Prodrugs for enhancement of lipophilicity. Recent Advancement in Prodrugs, 93–111. doi: 10.1201/9780429328275.
   Google Scholar
• dos Santos Lima, B., S. Shanmugam, J. d S. S. Quintans, L. J. Quintans-Júnior, and A. A. de Souza Araújo. 2019. Inclusion complex with cyclodextrins enhances the bioavailability of flavonoid compounds: A systematic review. Phytochemistry Reviews 18 (5):1337–59. doi: 10.1007/s11101-019-09650-y.
   Web of Science ®Google Scholar
• E Orhan, I., S. F. Nabavi, M. Daglia, G. C. Tenore, K. Mansouri, and S. M. Nabavi. 2015. Naringenin and atherosclerosis: A review of literature. Current Pharmaceutical Biotechnology 16 (3):245–51. doi: 10.2174/1389201015666141202110216.
   PubMed Web of Science ®Google Scholar
• Fang, J. 2014. Bioavailability of anthocyanins. Drug Metabolism Reviews 46 (4):508–20. doi: 10.3109/03602532.2014.978080.
   PubMed Web of Science ®Google Scholar
• Fernandes, I., A. Faria, V. de Freitas, C. Calhau, and N. Mateus. 2015. Multiple-approach studies to assess anthocyanin bioavailability. Phytochemistry Reviews 14 (6):899–919. doi: 10.1007/s11101-015-9415-3.
   Web of Science ®Google Scholar
• Gan, R.-Y., H.-B. Li, Z.-Q. Sui, and H. Corke. 2018. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Critical Reviews in Food Science and Nutrition 58 (6):924–41. doi: 10.1080/10408398.2016.1231168.
   PubMed Web of Science ®Google Scholar
• George, V. C., G. Dellaire, and H. V. Rupasinghe. 2017. Plant flavonoids in cancer chemoprevention: Role in genome stability. The Journal of Nutritional Biochemistry 45:1–14. doi: 10.1016/j.jnutbio.2016.11.007.
   PubMed Web of Science ®Google Scholar
• Gong, H., B-k Zhang, M. Yan, P-f Fang, H-d Li, C-p Hu, Y. Yang, P. Cao, P. Jiang, and X-r Fan. 2015. A protective mechanism of licorice (Glycyrrhiza uralensis): Isoliquiritigenin stimulates detoxification system via Nrf2 activation. Journal of Ethnopharmacology 162:134–9. doi: 10.1016/j.jep.2014.12.043.
   PubMed Web of Science ®Google Scholar
• Gonzales, G. B., G. Smagghe, C. Grootaert, M. Zotti, K. Raes, and J. V. Camp. 2015. Flavonoid interactions during digestion, absorption, distribution and metabolism: A sequential structure-activity/property relationship-based approach in the study of bioavailability and bioactivity. Drug Metabolism Reviews 47 (2):175–90. doi: 10.3109/03602532.2014.1003649.
   PubMed Web of Science ®Google Scholar
• Gujar, K., and S. Wairkar. 2020. Nanocrystal technology for improving therapeutic efficacy of flavonoids. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 71:153240. doi: 10.1016/j.phymed.2020.153240.
   PubMed Web of Science ®Google Scholar
• Guo, A., L. Qingchuan, H. Zhengming, Z. Yong, and L. Changxiao. 2015. In vitro inhibition of human P450 isoenzyme by hyperoside and preliminary analysis of metabolites in urine samples after intragastric administration in rats. China Journal of Traditional Chinese Medicine and Pharmacy 30 (10):3705–8.
   Google Scholar
• Hu, M., B. Wu, and Z. Liu. 2017. Bioavailability of polyphenols and flavonoids in the era of precision medicine. Mol. Pharmaceutics 14 (9):2861–2863. doi: 10.1021/acs.molpharmaceut.7b00545.
   Google Scholar
• Huaxiang, D., L. Ming, F. Ming, W. Kejian, and H. Guiqiong. 2019. Glycyrrhizin protects Alzheimer's disease through anti-inflammatory effects. Immunological Journal 35 (04):327–33. doi: 10.13431/j.cnki.immunol.j.20190051.
   Google Scholar
• Ichiyanagi, T., Y. Shida, M. M. Rahman, Y. Hatano, and T. Konishi. 2006. Bioavailability and tissue distribution of anthocyanins in bilberry (Vaccinium myrtillus L.) extract in rats. Journal of Agricultural and Food Chemistry 54 (18):6578–87. doi: 10.1021/jf0602370.
   PubMed Web of Science ®Google Scholar
• Ji, Y., B. Li, M. Qiao, J. Li, H. Xu, L. Zhang, and X. Zhang. 2020. Advances on the in vivo and in vitro glycosylations of flavonoids. Applied Microbiology and Biotechnology 104 (15):6587–14. doi: 10.1007/s00253-020-10667-z.
   PubMed Web of Science ®Google Scholar
• Jia, X., J. Chen, H. Lin, and M. Hu. 2004. Disposition of flavonoids via enteric recycling: Enzyme-transporter coupling affects metabolism of biochanin A and formononetin and excretion of their phase II conjugates. Journal of Pharmacology and Experimental Therapeutics 310 (3):1103–13. doi: 10.1124/jpet.104.068403.
   PubMed Web of Science ®Google Scholar
• Jiang, F. 2014. Pharmacology of polyphenols in cardiac remodeling: Potential biological mechanisms. In Polyphenols in human health and disease, eds R. R. Watson, V. R. Preedy and S. Zibadi, 947–62. Cambridge: Elsevier. doi: 10.1016/B978-0-12-398456-2.00073-6.
   Google Scholar
• Jianqiao, L., M. Ying, and Z. Yanhua. 2017. Research progress of silymarin Sustained-release preparation. China Pharmacy 28 (28):4011–4. doi: 10.6039/j.issn.1001-0408.2017.28.33.
   Google Scholar
• Jo, J. H., J. J. Jo, J. M. Lee, and S. Lee. 2016. Identification of absolute conversion to geraldol from fisetin and pharmacokinetics in mouse. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 1038:95–100. doi: 10.1016/j.jchromb.2016.10.034.
   PubMed Web of Science ®Google Scholar
• Jung, C. H., J. E. Jang, and J.-Y. Park. 2014. A novel therapeutic agent for type 2 diabetes mellitus: SGLT2 inhibitor. Diabetes & Metabolism Journal 38 (4):261–73. doi: 10.4093/dmj.2014.38.4.261.
   PubMedGoogle Scholar
• Kadari, A., S. Gudem, H. Kulhari, M. M. Bhandi, R. M. Borkar, V. R. Kolapalli, and R. Sistla. 2017. Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles. Drug Delivery 24 (1):224–32. doi: 10.1080/10717544.2016.1245366.
   PubMed Web of Science ®Google Scholar
• Kaşıkcı, M. B., and N. Bağdatlıoğlu. 2016. Bioavailability of quercetin. Current Research in Nutrition and Food Science Journal 4:146–51. doi: 10.12944/CRNFSJ.4.Special-Issue-October.20.
   Google Scholar
• Kaur, H., and G. Kaur. 2014. A critical appraisal of solubility enhancement techniques of polyphenols. Journal of Pharmaceutics 2014:180845. doi: 10.1155/2014/180845.
   PubMedGoogle Scholar
• Khan, H., H. Ullah, M. Martorell, S. E. Valdes, T. Belwal, S. Tejada, A. Sureda, and M. A. Kamal. 2021. Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Seminars in Cancer Biology 69:200–11. doi: 10.1016/j.semcancer.2019.07.023.
   PubMed Web of Science ®Google Scholar
• Kim, K., T. M. Vance, and O. K. Chun. 2016. Estimated intake and major food sources of flavonoids among US adults: Changes between 1999-2002 and 2007-2010 in NHANES. European Journal of Nutrition 55 (2):833–43. doi: 10.1007/s00394-015-0942-x.
   PubMed Web of Science ®Google Scholar
• Kim, S.-B., I.-S. Yoon, K.-S. Kim, S.-J. Cho, Y. S. Kim, H.-J. Cho, S.-J. Chung, S. Chong, and D.-D. Kim. 2014. In vitro and in vivo evaluation of the effect of puerarin on hepatic cytochrome p450-mediated drug metabolism. Planta Medica 80 (7):561–7. doi: 10.1055/s-0034-1368350.
   PubMed Web of Science ®Google Scholar
• Kopecna-Zapletalova, M., K. Krasulova, P. Anzenbacher, P. Hodek, and E. Anzenbacherova. 2017. Interaction of isoflavonoids with human liver microsomal cytochromes P450: Inhibition of CYP enzyme activities. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 47 (4):324–31. doi: 10.1080/00498254.2016.1195028.
   PubMed Web of Science ®Google Scholar
• Li, X., J.-M. Huang, J.-N. Wang, X.-K. Xiong, X.-F. Yang, and F. Zou. 2015. Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53. Chemico-Biological Interactions 232:12–20. doi: 10.1016/j.cbi.2015.03.003.
   PubMed Web of Science ®Google Scholar
• Li, X., J. K. Yun, and J. S. Choi. 2007. Effects of morin on the pharmacokinetics of etoposide in rats. Biopharmaceutics & Drug Disposition 28 (3):151–6. doi: 10.1002/bdd.539.
   PubMed Web of Science ®Google Scholar
• Li, Y., W. Qi, X. Song, S. Lv, H. Zhang, and Q. Yang. 2016. Huaier extract suppresses breast cancer via regulating tumor-associated macrophages. Scientific Reports 6:20049. doi: 10.1038/srep20049.
   PubMed Web of Science ®Google Scholar
• Li, Y., S. Sun, Q. Chang, L. Zhang, G. Wang, W. Chen, X. Miao, and Y. Zheng. 2013. A strategy for the improvement of the bioavailability and antiosteoporosis activity of BCS IV flavonoid glycosides through the formulation of their lipophilic aglycone into nanocrystals. Molecular Pharmaceutics 10 (7):2534–42. doi: 10.1021/mp300688t.
   PubMed Web of Science ®Google Scholar
• Liao, D., X. Liu, W. Dai, T. Tang, G. Ou, K. Zhang, M. Han, R. Kang, S. Yang, and D. Xiang. 2015. N-trimethyl chitosan (TMC)-modified microemulsions for improved oral bioavailability of puerarin: Preparation and evaluation. Drug Deliv 22 (4):516–21. doi: 10.3109/10717544.2013.879398.
   PubMed Web of Science ®Google Scholar
• Lin, J., L. M. Teo, L. P. Leong, and W. Zhou. 2019. In vitro bioaccessibility and bioavailability of quercetin from the quercetin-fortified bread products with reduced glycemic potential. Food Chemistry 286:629–35. doi: 10.1016/j.foodchem.2019.01.199.
   PubMed Web of Science ®Google Scholar
• Lin, J., and Z. Yumei. 2017. Effect of food on pharmacokinetics of catechin in Chinese healthy volunteers. Food and Drug 19 (01):1–7.
   Google Scholar
• Liping, D., L. Wei, Z. Hongyi, L. Guirong, H. Yan, H. Yicheng, S. Yu, and Z. Liang. 2019. Study on preparation and pharmacokinetics of puerarin microemulsion based on phase I metabolic regulation. China Pharmacy 30 (11):1459–64. doi: 10.6039/j.issn.1001-0408.2019.11.05.
   Google Scholar
• Liu, H., Y.-J. Wang, L. Yang, M. Zhou, M.-W. Jin, G.-S. Xiao, Y. Wang, H.-Y. Sun, and G.-R. Li. 2016. Synthesis of a highly water-soluble acacetin prodrug for treating experimental atrial fibrillation in beagle dogs. Scientific Reports 6:25743. doi: 10.1038/srep25743.
   PubMed Web of Science ®Google Scholar
• Liu, M., C. Hong, Y. Yao, H. Shen, G. Ji, G. Li, and Y. Xie. 2016. Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals. European Journal of Pharmaceutics and Biopharmaceutics 107:151–9. doi: 10.1016/j.ejpb.2016.07.008.
   PubMed Web of Science ®Google Scholar
• Lorenz, M., N. Jochmann, A. von Krosigk, P. Martus, G. Baumann, K. Stangl, and V. Stangl. 2007. Addition of milk prevents vascular protective effects of tea. European Heart Journal 28 (2):219–23. doi: 10.1093/eurheartj/ehl442.
   PubMed Web of Science ®Google Scholar
• Lu, H., H. Yao, R. Zou, X. Chen, and H. Xu. 2019. Galangin suppresses renal inflammation via the inhibition of NF-κB, PI3K/AKT and NLRP3 in uric acid treated NRK-52E tubular epithelial cells. BioMed Research International 2019:3018357. doi: 10.1155/2019/3018357.
   PubMed Web of Science ®Google Scholar
• Madunić, J., I. V. Madunić, G. Gajski, J. Popić, and V. Garaj-Vrhovac. 2018. Apigenin: A dietary flavonoid with diverse anticancer properties. Cancer Letters 413:11–22. doi: 10.1016/j.canlet.2017.10.041.
   PubMed Web of Science ®Google Scholar
• Maher, S., D. J. Brayden, L. Casettari, and L. Illum. 2019. Application of permeation enhancers in oral delivery of macromolecules: An update. Pharmaceutics 11 (1):41. doi: 10.3390/pharmaceutics11010041.
   PubMed Web of Science ®Google Scholar
• Manach, C., G. Williamson, C. Morand, A. Scalbert, and C. Rémésy. 2005. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American Journal of Clinical Nutrition 81 (1 Suppl):230S–42S. doi: 10.1093/ajcn/81.1.230S.
   PubMed Web of Science ®Google Scholar
• Mani, R., and V. Natesan. 2018. Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry 145:187–96. doi: 10.1016/j.phytochem.2017.09.016.
   PubMed Web of Science ®Google Scholar
• Martínez-Pérez, C., C. Ward, A. K. Turnbull, P. Mullen, G. Cook, J. Meehan, E. J. Jarman, P. I. T. Thomson, C. J. Campbell, D. McPhail, et al. 2016. Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models. British Journal of Cancer 114 (8):905–16. doi: 10.1038/bjc.2016.6.
   PubMed Web of Science ®Google Scholar
• Monobe, M., K. Ema, Y. Tokuda, and M. Maeda-Yamamoto. 2011. Increased plasma concentration of epigallocatechin in mice after orally administering a green tea (Camellia sinensis L.) extract supplemented by steamed rice. Bioscience, Biotechnology, and Biochemistry 75 (1):152–4. doi: 10.1271/bbb.100593.
   PubMed Web of Science ®Google Scholar
• Nabavi, S. F., N. Braidy, S. Habtemariam, I. E. Orhan, M. Daglia, A. Manayi, O. Gortzi, and S. M. Nabavi. 2015. Neuroprotective effects of chrysin: From chemistry to medicine. Neurochemistry International 90:224–31. doi: 10.1016/j.neuint.2015.09.006.
   PubMed Web of Science ®Google Scholar
• Németh, K., G. W. Plumb, J.-G. Berrin, N. Juge, R. Jacob, H. Y. Naim, G. Williamson, D. M. Swallow, and P. A. Kroon. 2003. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. European Journal of Nutrition 42 (1):29–42. doi: 10.1007/s00394-003-0397-3.
   PubMed Web of Science ®Google Scholar
• Ng, C. L., S.-E. Lee, J.-K. Lee, T.-H. Kim, W. S. Jang, J.-S. Choi, Y.-H. Kim, J.-K. Kim, and J.-S. Park. 2016. Solubilization and formulation of chrysosplenol C in solid dispersion with hydrophilic carriers. International Journal of Pharmaceutics 512 (1):314–21. doi: 10.1016/j.ijpharm.2016.08.062.
   PubMed Web of Science ®Google Scholar
• Nielsen, I. L. F., W. S. Chee, L. Poulsen, E. Offord-Cavin, S. E. Rasmussen, H. Frederiksen, M. Enslen, D. Barron, M.-N. Horcajada, and G. Williamson. 2006. Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: A randomized, double-blind, crossover trial. The Journal of Nutrition 136 (2):404–8. doi: 10.1093/jn/136.2.404.
   PubMed Web of Science ®Google Scholar
• Niu, M., W. Cai, H. Liu, Y. Chong, W. Hu, S. Gao, Q. Shi, X. Zhou, X. Liu, and R. Yu. 2015. Plumbagin inhibits growth of gliomas in vivo via suppression of FOXM1 expression. Journal of Pharmacological Sciences 128 (3):131–6. doi: 10.1016/j.jphs.2015.06.005.
   PubMed Web of Science ®Google Scholar
• Oostendorp, R. L., J. H. Beijnen, and J. H. Schellens. 2009. The biological and clinical role of drug transporters at the intestinal barrier. Cancer Treatment Reviews 35 (2):137–47. doi: 10.1016/j.ctrv.2008.09.004.
   PubMed Web of Science ®Google Scholar
• Oteiza, P., C. G. Fraga, D. Mills, and D. Taft. 2018. Flavonoids and the gastrointestinal tract: Local and systemic effects. Molecular Aspects of Medicine 61:41–9. doi: 10.1016/j.mam.2018.01.001.
   PubMed Web of Science ®Google Scholar
• Pan, M.-H., C.-S. Lai, and C.-T. Ho. 2010. Anti-inflammatory activity of natural dietary flavonoids. Food & Function 1 (1):15–31. doi: 10.1039/c0fo00103a.
   PubMed Web of Science ®Google Scholar
• Pengfei, J. 2012. Study on cardiovascular protective effects of phloretin. Journal of Modern Medicine & Health 28 (09):1284–6.
   Google Scholar
• Piao, L., M. Zang, Y. Gu, and B. Liu. 2017. Development and validation of a sensitive UHPLC–MS/MS method for quantitative analysis of farrerol in rat plasma: Application to pharmacokinetic and bioavailability studies. Biomedical Chromatography 31 (11):e4005. doi: 10.1002/bmc.4005.
   Web of Science ®Google Scholar
• Qiao, H., X. Zhang, T. Wang, L. Liang, W. Chang, and H. Xia. 2014. Pharmacokinetics, biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration. Pharmaceutical Biology 52 (2):228–36. doi: 10.3109/13880209.2013.832334.
   PubMed Web of Science ®Google Scholar
• Qinquan, L., Z. Qiang, N. Junqi, and G. Yanhang. 2015. New advances in pharmacological mechanism of silymarin and re-investigation of its clinical values. Journal of Clinical Hepatology 31 (02):315–7. doi: 10.3969/j.issn.1001-5256.2015.02.044.
   Google Scholar
• Qiuxin, W., W. Hui, L. Dongmei, and B. Hongsheng. 2019. Application of epigallocatechin gallate (EGCG) in ophthalmic research. New Progress in Ophthalmology 39 (03):287–90. doi: 10.13389/j.cnki.rao.2019.0065.
   Google Scholar
• Ravi, G., R. N. Charyulu, A. Dubey, P. Prabhu, S. Hebbar, and A. C. Mathias. 2018. Nano-lipid complex of rutin: Development, characterisation and in vivo investigation of hepatoprotective, antioxidant activity and bioavailability study in rats. AAPS PharmSciTech 19 (8):3631–49. doi: 10.1208/s12249-018-1195-9.
   PubMed Web of Science ®Google Scholar
• Reinboth, M., S. Wolffram, G. Abraham, F. R. Ungemach, and R. Cermak. 2010. Oral bioavailability of quercetin from different quercetin glycosides in dogs. The British Journal of Nutrition 104 (2):198–203. doi: 10.1017/S000711451000053X.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Mateos, A., M. J. Oruna-Concha, C. Kwik-Uribe, A. Vidal, and J. P. Spencer. 2012. Influence of sugar type on the bioavailability of cocoa flavanols. The British Journal of Nutrition 108 (12):2243–50. doi: 10.1017/S0007114512000475.
   PubMed Web of Science ®Google Scholar
• Rongjia, L., C. Junxiu, Z. Dexian, F. Yaowen, L. Wenli, and H. Xing. 2017. Study on the effect of isorhamnetin on human liver microsomal CYPs activity and rat primary hepatocyte toxicity. Drug Evaluation Research 40 (05):627–32. doi: 10.7501/j.issn.1674-6376.2017.05.008.
   Google Scholar
• Roth, M., B. N. Timmermann, and B. Hagenbuch. 2011. Interactions of green tea catechins with organic anion-transporting polypeptides. Drug Metabolism and Disposition: The Biological Fate of Chemicals 39 (5):920–6. doi: 10.1124/dmd.110.036640.
   PubMed Web of Science ®Google Scholar
• Rüfer, C. E., A. Bub, J. Möseneder, P. Winterhalter, M. Stürtz, and S. E. Kulling. 2008. Pharmacokinetics of the soybean isoflavone daidzein in its aglycone and glucoside form: A randomized, double-blind, crossover study. The American Journal of Clinical Nutrition 87 (5):1314–23. doi: 10.1093/ajcn/87.5.1314.
   PubMed Web of Science ®Google Scholar
• Ruge, C., K. Yutaro, N. Airi, M. Yuji, T. Kazunari, T. Takashi, and M. Toshiro. 2015. NMR spectroscopic and quantum mechanical analyses of enhanced solubilization of hesperidin by theasinensin A. Pharmaceutical Research 32 (7):2301–2309. doi: 10.1007/s11095-015-1621-6.
   PubMed Web of Science ®Google Scholar
• S Qian, Y., S. Ramamurthy, M. Candasamy, S. Md, R. H Kumar, and V. S Meka. 2016. Production, characterization and evaluation of kaempferol nanosuspension for improving oral bioavailability. Current Pharmaceutical Biotechnology 17 (6):549–55. doi: 10.2174/1389201017666160127110609.
   PubMed Web of Science ®Google Scholar
• Salehi, B., P. V. T. Fokou, M. Sharifi-Rad, P. Zucca, R. Pezzani, N. Martins, and J. Sharifi-Rad. 2019. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals 12 (1):11. doi: 10.3390/ph12010011.
   Web of Science ®Google Scholar
• Sarawek, S., H. Derendorf, and V. Butterweck. 2008. Pharmacokinetics of luteolin and metabolites in rats. Natural Product Communications 3 (12):1934578X0800301. doi: 10.1177/1934578X0800301218.
   Web of Science ®Google Scholar
• Shen, B., N. Wu, C. Shen, F. Zhang, Y. Wu, P. Xu, L. Zhang, W. Wu, Y. Lu, J. Han, et al. 2016. Hyperoside nanocrystals for HBV treatment: Process optimization, in vitro and in vivo evaluation. Drug Development and Industrial Pharmacy 42 (11):1772–81. doi: 10.3109/03639045.2016.1173051.
   PubMed Web of Science ®Google Scholar
• Sonali, D., S. Tejal, T. Vaishali, and G. Tejal. 2010. Silymarin-solid dispersions: Characterization and influence of preparation methods on dissolution. Acta Pharmaceutica 60 (4):427–43. doi: 10.2478/v10007-010-0038-3.
   PubMed Web of Science ®Google Scholar
• Srinivas, N. R. 2015. Recent trends in preclinical drug-drug interaction studies of flavonoids-Review of case studies, issues and perspectives. Phytotherapy Research: PTR 29 (11):1679–91. doi: 10.1002/ptr.5447.
   PubMed Web of Science ®Google Scholar
• Surampalli, G., B. K. Nanjwade, and P. Patil. 2016. Safety evaluation of naringenin upon experimental exposure on rat gastrointestinal epithelium for novel optimal drug delivery. Drug Delivery 23 (2):512–24. doi: 10.3109/10717544.2014.923957.
   PubMed Web of Science ®Google Scholar
• Ta, N., and T. Walle. 2007. Aromatase inhibition by bioavailable methylated flavones. The Journal of Steroid Biochemistry and Molecular Biology 107 (1-2):127–9. doi: 10.1016/j.jsbmb.2007.01.006.
   PubMed Web of Science ®Google Scholar
• Taneja, I., S. Arora, R. Raju, K. Siva, and N. Siddiqui. 2013. Disposition of pharmacologically active dietary isoflavones in biological systems. Current Drug Metabolism 14 (4):369–80. doi: 10.2174/1389200211314040002.
   PubMed Web of Science ®Google Scholar
• Teng, H., and L. Chen. 2019. Polyphenols and bioavailability: An update. Critical Reviews in Food Science and Nutrition 59 (13):2040–51. doi: 10.1080/10408398.2018.1437023.
   PubMed Web of Science ®Google Scholar
• Terao, J. 2017. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function. Biochemical Pharmacology 139:15–23. doi: 10.1016/j.bcp.2017.03.021.
   PubMed Web of Science ®Google Scholar
• Thakur, N., P. Raigond, Y. Singh, T. Mishra, B. Singh, M. K. Lal, and S. Dutt. 2020. Recent updates on bioaccessibility of phytonutrients. Trends in Food Science & Technology 97:366–80. doi: 10.1016/j.tifs.2020.01.019.
   Web of Science ®Google Scholar
• Thilakarathna, S. H., and H. Rupasinghe. 2013. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 5 (9):3367–87. doi: 10.3390/nu5093367.
   PubMed Web of Science ®Google Scholar
• Tsuji, P. A., and T. Walle. 2007. Benzo[a]pyrene-induced cytochrome P450 1A and DNA binding in cultured trout hepatocytes - inhibition by plant polyphenols. Chemico-Biological Interactions 169 (1):25–31. doi: 10.1016/j.cbi.2007.05.001.
   PubMed Web of Science ®Google Scholar
• van Duynhoven, J., E. E. Vaughan, D. M. Jacobs, R. A. Kemperman, E. J. J. van Velzen, G. Gross, L. C. Roger, S. Possemiers, A. K. Smilde, J. Dore, et al. 2011. Metabolic fate of polyphenols in the human superorganism. Proceedings of the National Academy of Sciences 108 (Supplement_1):4531–8. doi: 10.1073/pnas.1000098107.
   PubMedGoogle Scholar
• Vanzo, A., U. Vrhovsek, F. Tramer, F. Mattivi, and S. Passamonti. 2011. Exceptionally fast uptake and metabolism of cyanidin 3-glucoside by rat kidneys and liver. Journal of Natural Products 74 (5):1049–54. doi: 10.1021/np100948a.
   PubMed Web of Science ®Google Scholar
• Walle, T., N. Ta, T. Kawamori, X. Wen, P. A. Tsuji, and U. K. Walle. 2007. Cancer chemopreventive properties of orally bioavailable flavonoids-methylated versus unmethylated flavones. Biochemical Pharmacology 73 (9):1288–96. doi: 10.1016/j.bcp.2006.12.028.
   PubMed Web of Science ®Google Scholar
• Wan, M. L. Y., V. A. Co, and H. El-Nezami. 2021. Dietary polyphenol impact on gut health and microbiota. Critical Reviews in Food Science and Nutrition 61 (4):690–22. doi: 10.1080/10408398.2020.1744512.
   PubMed Web of Science ®Google Scholar
• Wang, H., Y. Cui, Q. Fu, B. Deng, G. Li, J. Yang, T. Wu, and Y. Xie. 2015. A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Development and Industrial Pharmacy 41 (10):1693–703. doi: 10.3109/03639045.2014.991402.
   PubMed Web of Science ®Google Scholar
• Wang, L., W. Wei, Q. Xiao, H. Yang, and X. Ci. 2019. Farrerol ameliorates APAP-induced hepatotoxicity via activation of Nrf2 and autophagy. International Journal of Biological Sciences 15 (4):788–99. doi: 10.7150/ijbs.30677.
   PubMed Web of Science ®Google Scholar
• Wang, Q., J. Huang, C. Hu, N. Xia, T. Li, and Q. Xia. 2017. Stabilization of a non-aqueous self-double-emulsifying delivery system of rutin by fat crystals and nonionic surfactants: Preparation and bioavailability study. Food & Function 8 (7):2512–22. doi: 10.1039/C7FO00439G.
   PubMed Web of Science ®Google Scholar
• Wang, S., H. Wei, M. Cai, Y. Lu, W. Hou, Q. Yang, H. Dong, and L. Xiong. 2014. Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice. International Journal of Biological Sciences 10 (4):457–65. doi: 10.7150/ijbs.7562.
   PubMed Web of Science ®Google Scholar
• Wang, T.-y., Q. Li, and K.-s. Bi. 2018. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian Journal of Pharmaceutical Sciences 13 (1):12–23. doi: 10.1016/j.ajps.2017.08.004.
   PubMed Web of Science ®Google Scholar
• Wang, Z., Y. Lan, M. Chen, C. Wen, Y. Hu, Z. Liu, and L. Ye. 2017. Eriodictyol, not its glucuronide metabolites, attenuates acetaminophen-induced hepatotoxicity. Molecular Pharmaceutics 14 (9):2937–51. doi: 10.1021/acs.molpharmaceut.7b00345.
   PubMed Web of Science ®Google Scholar
• Wong, C. C., Y. Akiyama, T. Abe, J. D. Lippiat, C. Orfila, and G. Williamson. 2012. Carrier-mediated transport of quercetin conjugates: Involvement of organic anion transporters and organic anion transporting polypeptides. Biochemical Pharmacology 84 (4):564–70. doi: 10.1016/j.bcp.2012.05.011.
   PubMed Web of Science ®Google Scholar
• Wu, L., J. Liu, W. Han, X. Zhou, X. Yu, Q. Wei, S. Liu, and L. Tang. 2015. Time-dependent metabolism of luteolin by human UDP-glucuronosyltransferases and its intestinal first-pass glucuronidation in mice. Journal of Agricultural and Food Chemistry 63 (39):8722–33. doi: 10.1021/acs.jafc.5b02827.
   PubMed Web of Science ®Google Scholar
• Wu, X., W. Ge, T. Shao, W. Wu, J. Hou, L. Cui, J. Wang, and Z. Zhang. 2017. Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630. International Journal of Nanomedicine 12:1475–83. doi: 10.2147/IJN.S125041.
   PubMed Web of Science ®Google Scholar
• Xia, E., X. He, H. Li, S. Wu, S. Li, and G. Deng. 2014. Chapter 5—Biological activities of polyphenols from grapes. In Polyphenols in human health and disease, 1:47–58. doi: 10.1016/B978-0-12-398456-2.00005-0.
   Google Scholar
• Xiao, J., and G. Kai. 2012. A review of dietary polyphenol-plasma protein interactions: Characterization, influence on the bioactivity, and structure-affinity relationship. Critical Reviews in Food Science and Nutrition 52 (1):85–101. doi: 10.1080/10408398.2010.499017.
   PubMed Web of Science ®Google Scholar
• Xiao, J., F. Mao, F. Yang, Y. Zhao, C. Zhang, and K. Yamamoto. 2011. Interaction of dietary polyphenols with bovine milk proteins: Molecular structure-affinity relationship and influencing bioactivity aspects. Molecular Nutrition & Food Research 55 (11):1637–45. doi: 10.1002/mnfr.201100280.
   PubMed Web of Science ®Google Scholar
• Xiao, L., T. Yi, M. Chen, C. W. K. Lam, and H. Zhou. 2016. A new mechanism for increasing the oral bioavailability of scutellarin with Cremophor EL: Activation of MRP3 with concurrent inhibition of MRP2 and BCRP. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 93:456–67. doi: 10.1016/j.ejps.2016.08.054.
   PubMed Web of Science ®Google Scholar
• Xie, Y., H. Luo, J. Duan, C. Hong, P. Ma, G. Li, T. Zhang, T. Wu, and G. Ji. 2014. Phytic acid enhances the oral absorption of isorhamnetin, quercetin, and kaempferol in total flavones of Hippophae rhamnoides L. Fitoterapia 93:216–25. doi: 10.1016/j.fitote.2014.01.013.
   PubMed Web of Science ®Google Scholar
• Yamamoto, A., H. Ukai, M. Morishita, and H. Katsumi. 2020. Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs. Pharmacology & Therapeutics 211:107537. doi: 10.1016/j.pharmthera.2020.107537.
   PubMed Web of Science ®Google Scholar
• Yang, C.-J., Z.-B. Wang, Y.-Y. Mi, M.-J. Gao, J.-N. Lv, Y.-H. Meng, B.-Y. Yang, and H.-X. Kuang. 2016. UHPLC-MS/MS determination, pharmacokinetic, and bioavailability study of taxifolin in rat plasma after oral administration of its nanodispersion. Molecules (Basel, Switzerland) 21 (4):494. doi: 10.3390/molecules21040494.
   PubMed Web of Science ®Google Scholar
• Yang, P., F. Xu, H. F. Li, Y. Wang, F. C. Li, M. Y. Shang, G. X. Liu, X. Wang, and S. Q. Cai. 2016. Detection of 191 taxifolin metabolites and their distribution in rats using HPLC-ESI-IT-TOF-MS(n). Molecules 21 (9):1209. doi: 10.3390/molecules21091209.
   Web of Science ®Google Scholar
• Yang, Z., K. Kulkarni, W. Zhu, and M. Hu. 2012. Bioavailability and pharmacokinetics of genistein: Mechanistic studies on its ADME. Anti-Cancer Agents in Medicinal Chemistry 12 (10):1264–80. doi: 10.2174/1871520803833107.
   PubMed Web of Science ®Google Scholar
• You, H. S., J. F. Xing, J. Lu, W. H. Dong, J. T. Liu, and Y. L. Dong. 2014. Influence of the gastrointestinal microflora and efflux transporters on the absorption of scutellarin and scutellarein. Phytotherapy Research: PTR 28 (9):1295–300. doi: 10.1002/ptr.5127.
   PubMed Web of Science ®Google Scholar
• Zabela, V., C. Sampath, M. Oufir, F. Moradi-Afrapoli, V. Butterweck, and M. Hamburger. 2016. Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats. Fitoterapia 115:189–97. doi: 10.1016/j.fitote.2016.10.008.
   PubMed Web of Science ®Google Scholar
• Zhang, K., L. Gu, J. Chen, Y. Zhang, Y. Jiang, L. Zhao, K. Bi, and X. Chen. 2015. Preparation and evaluation of kaempferol-phospholipid complex for pharmacokinetics and bioavailability in SD rats. Journal of Pharmaceutical and Biomedical Analysis 114:168–75. doi: 10.1016/j.jpba.2015.05.017.
   PubMed Web of Science ®Google Scholar
• Zhang, Q., F. Zhang, K. Thakur, J. Wang, H. Wang, F. Hu, J.-G. Zhang, and Z.-J. Wei. 2018. Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 112:466–75. doi: 10.1016/j.fct.2017.07.002.
   PubMed Web of Science ®Google Scholar
• Zhankun, H., and T. Fang. 2011. Study on intestinal absorption kinetics of hesperidin by valgus intestinal sac. China Journal of Chinese Materia Medica 36 (18):2576–8.
   Google Scholar
• Zhao, J., J. Yang, and Y. Xie. 2019. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. International Journal of Pharmaceutics 570:118642. doi: 10.1016/j.ijpharm.2019.118642.
   PubMed Web of Science ®Google Scholar
• Zhou, Y., W. Dong, J. Ye, H. Hao, J. Zhou, R. Wang, and Y. Liu. 2017. A novel matrix dispersion based on phospholipid complex for improving oral bioavailability of baicalein: Preparation, in vitro and in vivo evaluations. Drug Delivery 24 (1):720–8. doi: 10.1080/10717544.2017.1311968.
   PubMed Web of Science ®Google Scholar