The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites

Silberberg, M.; Morand, C.; Mathevon, T.; Besson, C.; Manach, C.; Scalbert, A.; Remesy, C.

doi:10.1007/s00394-005-0568-5

Cited by 164Phytochemicals and Antioxidant ActivitiesNutrition, Genetics, and DiseaseFlavonoids in Medical Research

The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites

Silberberg, M., Morand, C., Mathevon, T., Besson, C., Manach, C., Scalbert, A., Remesy, C.·2006·European Journal of Nutrition

DOI 10.1007/s00394-005-0568-5

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Abstract

Background After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability.Aim of the study The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 microM).Methods The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC.Results Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 microM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine.Conclusion Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.

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The yield of phase I/II reactions is often very high, and host-transformed metabolites retain many features of their parent compounds.
“The yield of phase I/II reactions are often very high (68,71), and host-transformed metabolites retain many of the features of their parent compounds.”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [71]

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Glyoxalase 1 Modulation in Obesity and Diabetes
Rabbani, N., & Thornalley, P. J. (2019) · Antioxidants & Redox Signaling · doi:10.1089/ars.2017.7424 · Cited by 102 · see citing works
“Studies of HESP infusion into the small intestine have shown that the absorptionof free HESP is limitedby thisconjugation thatis overwhelmed by 120 l M HESP, and increased unconjugated HESP is then absorbed (164).”
Phase II Metabolism of Hesperetin by Individual UDP-Glucuronosyltransferases and Sulfotransferases and Rat and Human Tissue Samples
Brand, W., Boersma, M. G., Bik, H., den Hil, E. F. H.-V., Vervoort, J. J. M., Barron, D., Meinl, W., Glatt, H. R., Williamson, G., van BLADEREN, P. J., et al. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.031047 · Cited by 99 · see citing works
“of hesperetin (Silberberg et al., 2006) and in its limited bioavailability”
Background
Unlocking Polyphenol Efficacy: The Role of Gut Microbiota in Modulating Bioavailability and Health Effects
Mahdi, L., Graziani, A., Baffy, G., Mitten, E. K., Portincasa, P., & Khalil, M. (2025) · Nutrients · doi:10.3390/nu17172793 · Cited by 97 · see citing works
“However, at higher doses (~120 µ M), this conjugation/secretion became saturated, reducing secretion and increasing systemic availability [173].”
Citrus flavonoids and the intestinal barrier: Interactions and effects
Wang, M., Zhao, H., Wen, X., Ho, C., & Li, S. (2020) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12652 · Cited by 94 · see citing works
Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism
Habauzit, V., Sacco, S. M., Gil‐Izquierdo, Á., Trzeciakiewicz, A., Morand, C., Barron, D., Pinaud, S., Offord, E., & Horcajada, M.-N. (2011) · Bone · doi:10.1016/j.bone.2011.07.030 · Cited by 86 · see citing works
“Concerning hesperetin and naringenin, these two flavanones have a quite similar chemical structure, lipophilicity and both presented a high intestinal and biliary secretion of their conjugated metabolites as previously shown in rats, using an in situ perfusionmodel [49,50].”
Background
Cocoa Polyphenols Inhibit Phorbol Ester-Induced Superoxide Anion Formation in Cultured HL-60 Cells and Expression of Cyclooxygenase-2 and Activation of NF-κB and MAPKs in Mouse Skin In Vivo
Lee, K. W., Kundu, J. K., Kim, S. O., Chun, K., Lee, H. J., & Surh, Y. (2006) · Journal of Nutrition · doi:10.1093/jn/136.5.1150 · Cited by 84 · see citing works
The molecular basis of nutritional intervention in multiple sclerosis: A narrative review
Riccio, P. (2011) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2011.06.006 · Cited by 83 · see citing works
Impact of olive oil phenolic concentration on human plasmatic phenolic metabolites
Rubió, L., Valls, R. M., Macià, A., Pedret, A., Giralt, M., Romero, M., de la Torre, R., Covas, M., Solà, R., & Motilva, M. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.07.085 · Cited by 80 · see citing works
“In this sense, results of in vitro and in vivo experimental studies showed that some saturation in the metabolism and absorption of phenols could occur (Hu, Chen & Lin, 2003; Silberberg et al., 2006).”
Result
Analysis of a whole diet in terms of phenolic content and antioxidant capacity: effects of a simulated gastrointestinal digestion
Koehnlein, E. A., Koehnlein, É. M., Corrêa, R. C. G., Nishida, V. S., Corrêa, V. G., Bracht, A., & Peralta, R. M. (2016) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2016.1186156 · Cited by 79 · see citing works
“The loss of phenolic compounds during the digestion process is unlikely due to interactions with digestive enzymes, but more probably caused by the chemical conditions prevailing during pancreatic digestion (Silberberg et al. 2006).”
Background
<i>In vitro</i>and<i>in vivo</i>small intestinal metabolism of CYP3A and UGT substrates in preclinical animals species and humans: species differences
Komura, H., & Iwaki, M. (2011) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.597401 · Cited by 78 · see citing works
“A similar efflux of conjugated metabolites in the rat intestine was found for genistein and hesperetin (Silberberg et al., 2006).”
Background
Pharmacokinetics of prenylflavonoids and correlations with the dynamics of estrogen action in sera following ingestion of a standardized Epimedium extract
Wong, S. P., Shen, P., Lee, L., Li, J., & Yong, E. (2009) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2009.04.022 · Cited by 75 · see citing works
Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells
Rastogi, H., & Jana, S. (2014) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-014-0234-5 · Cited by 74 · see citing works
“The in vitro methods include simple parallel artificial membrane permeability (PAMPA) or assays based on biological cell layers, e.g., Caco-2 cells (Kerns et al. 2004; Silberberg et al. 2006).”
Flavanone metabolism in healthy and tumor-bearing rats
Silberberg, M., Gil‐Izquierdo, Á., Combaret, L., Rémésy, C., Scalbert, A., & Morand, C. (2006) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2006.07.083 · Cited by 72 · see citing works
“The intestinal secretion of the conjugates back to the lumen limits their oral bioavailability [10,11].”
Background
Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment
Redan, B. W., Buhman, K. K., Novotny, J. A., & Ferruzzi, M. G. (2016) · Advances in Nutrition · doi:10.3945/an.116.013029 · Cited by 67 · see citing works
“Because the bioactivity of phenolic compounds is largely dependent on their metabolism by key phase II enzymes (52), it is necessary to consider the systems that may”
Background
Exploring the Molecular Pathways Behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications
Peron, G., Hidalgo‐Liberona, N., González‐Domínguez, R., Garcia‐Aloy, M., Guglielmetti, S., Bernardi, S., Kirkup, B. M., Kroon, P. A., Cherubini, A., Riso, P., et al. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b01687 · Cited by 64 · see citing works
Bioavailability of Dietary Polyphenols and the Cardiovascular Diseases
Shivashankara, K. S., & Acharya, S. N. (2010) · The Open Nutraceuticals Journal · doi:10.2174/1876396001003010227 · Cited by 66 · see citing works
“[83] reported that the extent of biliary and intestinal secretion into lumen as conjugates may indiFig.”
Background
Effects of in vitro digestion and in vitro colonic fermentation on stability and functional properties of yerba mate (Ilex paraguariensis A. St. Hil.) beverages
Corrêa, V. G., Gonçalves, G. A., de Sá‐Nakanishi, A. B., Ferreira, I. C. F. R., Barros, L., Días, M. I., Koehnlein, E. A., de Souza, C. G. M., Bracht, A., & Peralta, R. M. (2017) · Food Chemistry · doi:10.1016/j.foodchem.2017.05.125 · Cited by 64 · see citing works
“The loss of phenolic compounds during the digestion process is unlikely due to interactions with digestive enzymes, but most probably caused by the chemical conditions prevailing during pancreatic digestion (Silberberg et al., 2006).”
Background
In Vivo Pharmacokinetics of Hesperidin Are Affected by Treatment with Glucosidase-like BglA Protein Isolated from Yeasts
Li, Y., Li, X., Li, G., Du, W.-C., Zhang, J., Li, W., Xu, J., Hu, M., & Zhu, Z. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf800105c · Cited by 63 · see citing works
Bioavailability of a silybin–phosphatidylcholine complex in dogs
Filburn, C. R., KETTENACKER, R., & GRIFFIN, D. W. (2007) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2007.00834.x · Cited by 61 · see citing works
“The in vivo effectiveness of silymarin flavonolignans, as with many polyphenols, depends on bioavailability and achieving therapeutic concentrations in the organs of interest (Manach et al., 2004, 2005; Silberberg et al., 2006).”
Background
Regioselective O-Derivatization of Quercetin via Ester Intermediates. An Improved Synthesis of Rhamnetin and Development of a New Mitochondriotropic Derivative
Mattarei, A., Biasutto, L., Rastrelli, F., Garbisa, S., Marotta, E., Zoratti, M., & Paradisi, C. (2010) · Molecules · doi:10.3390/molecules15074722 · Cited by 60 · see citing works
“Despite the fact that several natural polyphenols are being exploited as additives in nutritional, cosmetic and over-the counter pharmacological formulations, their activity in vivo is difficult to demonstrate due to their low bioavailability [5–7].”
Background
Do short chain fatty acids and phenolic metabolites of the gut have synergistic anti-inflammatory effects? – New insights from a TNF-α-induced Caco-2 cell model
Zheng, S., Zhang, H., Liu, R., Huang, C.-L., Li, H., Deng, Z., & Tsao, R. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109833 · Cited by 59 · see citing works
Metabolic programming of the epigenome: host and gut microbial metabolite interactions with host chromatin
Krautkramer, K. A., Dhillon, R. S., Denu, J. M., & Carey, H. V. (2017) · Translational research · doi:10.1016/j.trsl.2017.08.005 · Cited by 58 · see citing works
“Plant polyphenols are found in various fruits, vegetables, nuts, and teas and undergo extensive transformations by the gut microbiota before entering enterohepatic circulation and undergoing further metabolism by the host.(152,153) Although these compounds have limited bioavailability and are found at low levels in pl…”
Exploitation of Polyphenolic Extracts from Grape Marc as Natural Antioxidants by Encapsulation in Lipid-Based Nanodelivery Systems
Sessa, M., Casazza, A. A., Perego, P., Tsao, R., Ferrari, G., & Donsı̀, F. (2012) · Food and Bioprocess Technology · doi:10.1007/s11947-012-0911-9 · Cited by 57 · see citing works
Deciphering the Role of Polyphenols in Sports Performance: From Nutritional Genomics to the Gut Microbiota toward Phytonutritional Epigenomics
Sorrenti, V., Fortinguerra, S., Caudullo, G., & Buriani, A. (2020) · Nutrients · doi:10.3390/nu12051265 · Cited by 55 · see citing works
Intestinal tract injury by drugs: Importance of metabolite delivery by yellow bile road
Treinen–Moslen, M., & Kanz, M. F. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.05.007 · Cited by 54 · see citing works
Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract
Gundala, S. R., Mukkavilli, R., Yang, C., Yadav, P., Tandon, V., Vangala, S., Prakash, S., & Aneja, R. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu011 · Cited by 52 · see citing works
“Recently, identification of a vast array of phenolic metabolites in circulation has offered useful insights and allowed us to realize and explore the bioavailability, especially of poorly absorbable compounds, such as the phenolics (12,13).”
Background
Effects of a Flavonoid-Rich Juice on Inflammation, Oxidative Stress, and Immunity in Elite Swimmers: A Metabolomics-Based Approach
Knab, A. M., Nieman, D. C., Gillitt, N. D., Shanely, R. A., Cialdella-Kam, L. A., Henson, D. A., & Sha, W. (2013) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.23.2.150 · Cited by 51 · see citing works
“The interaction between flavonoids from different subclasses increases their bioavailability and bioactivity (Silberberg et al., 2006).”
Background
Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides
Zeng, M., Sun, R., Basu, S., Ma, Y., Ge, S., Yin, T., Gao, S., Zhang, J., & Hu, M. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500692 · Cited by 51 · see citing works
Natural Polyphenols and Apoptosis Induction in Cancer Therapy
Estrela, L. R. M. (2013) · Journal of Carcinogenesis & Mutagenesis · doi:10.4172/2157-2518.s6-004 · Cited by 50 · see citing works
“Once absorbed, polyphenols are further metabolized in the liver [146] and then eliminated through urine and bile.”
Background
Apple juice intervention modulates expression of ARE-dependent genes in rat colon and liver
Soyalan, B., Minn, J., Schmitz, H., Schrenk, D., Will, F., Dietrich, H., Baum, M., Eisenbrand, G., & Janzowski, C. (2010) · European Journal of Nutrition · doi:10.1007/s00394-010-0124-9 · Cited by 48 · see citing works
“Moreover, the extent of polyphenol absorption in the small intestine, largely determined by chemical structure and nature/amount of metabolites formed by microflora, is a major influential factor [34, 35].”
Ferulic acid-4-O-sulfate rather than ferulic acid relaxes arteries and lowers blood pressure in mice
Rymenant, E. V., Camp, J. V., Pauwels, B., Boydens, C., Daele, L. V., Beerens, K., Brouckaert, P., Smagghe, G. J., Kerimi, A., Williamson, G., et al. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.02.018 · Cited by 48 · see citing works
“When FA was perfused into the rat small intestine, free FA was the major form present in the mesenteric vein (60%), but in aorta, 75% of the FA was conjugated [15], while only conjugated FA was found in plasma and bile [16].”
Background
Sutherlandia frutescens : The Meeting of Science and Traditional Knowledge
Aboyade, O. M., Styger, G., Gibson, D., & Hughes, G. D. (2013) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2012.0343 · Cited by 45 · see citing works
“…effects, including anticancer and antiviral 35 and antiosteoporotic and anticardiovascular activities 36 and anti-inﬂammatory and antiallergic, 37 antimicrobial, antiproliferative, chemoprotective, and antioxidant 38 effects, that may explain or support the traditional claims of S. frutescens…”
Dietary supplementation of ferulic acid to steers under commercial feedlot feeding conditions improves meat quality and shelf life
González‐Ríos, H., Dávila‐Ramírez, J. L., Peña‐Ramos, E. A., Valenzuela‐Melendres, M., Zamorano-García, L., Islava-Lagarda, T. Y., & Valenzuela-Grijalva, N. V. (2016) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2016.10.011 · Cited by 45 · see citing works
Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management
Nurcahyanti, A. D. R., Cokro, F., Wulanjati, M. P., Mahmoud, M. F., Wink, M., & Sobeh, M. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.891339 · Cited by 44 · see citing works
“Although clinical trials are challenging, especially introducing prebiotics and probiotics to modulate the gut microbiome, constant and in-depth studies must be performed as there are several differences in metabolic profiles determined by gut microbiota (193).”
Background
Hesperetin attenuates the highly reducing sugar-triggered inhibition of osteoblast differentiation
Choi, E. M., & Kim, Y. H. (2007) · Cell Biology and Toxicology · doi:10.1007/s10565-007-9031-0 · Cited by 44 · see citing works
“Silberberg et al. (2006) reported that the extent of enterohepatic cycling of the tested polyphenols (genistein, hesperetin, and ferulic acid) was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine.”
Background
Therapeutical properties of ferulic acid and bioavailability enhancement through feruloyl esterase
Palaniswamy, S. K., & Govindaswamy, V. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.06.013 · Cited by 44 · see citing works
Dietary Assumption of Plant Polyphenols and Prevention of Allergy
Chirumbolo, S. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990042 · Cited by 44 · see citing works
Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals
Barnes, R. C., Kim, H., Fang, C., Bennett, W. A., Nemec, M. J., Sirven, M. A., Suchodolski, J. S., Deutz, N. E. P., Britton, R. A., Mertens‐Talcott, S. U., et al. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800512 · Cited by 42 · see citing works
Flavonoids and Their Biological Secrets
Rashid, M. I., Fareed, M. I., Rashid, H., Aziz, H., Ehsan, N., Khalid, S., Ghaffar, I., Ali, R., Gul, A., & Hakeem, K. R. (2019) · Springer eBooks · doi:10.1007/978-3-030-03344-6_24 · Cited by 42 · see citing works
What is Xenohormesis?
Baur, J. A., & Sinclair, D. A. (2008) · American Journal of Pharmacology and Toxicology · doi:10.3844/ajptsp.2008.152.159 · Cited by 41 · see citing works
“But could mammals have evolved or maintained a system capable of making sense of the panoply of phytochemicals passing through our diets? Since the bioavailability of many plant molecules appears to be limited by their rapid metabolism, a mechanism for cooperative action between molecules may be as simple as tying up…”
Background
Structure-Dependent Inhibition of Gelatinases by Dietary Antioxidants in Rat Astrocytes and Sera of Multiple Sclerosis Patients
Liuzzi, G. M., Latronico, T., Branà, M. T., Gramegna, P., Coniglio, M. G., Rossano, R., Larocca, M., & Riccio, P. (2011) · Neurochemical Research · doi:10.1007/s11064-010-0373-2 · Cited by 40 · see citing works
“In foods, flavonoids are mainly glycosylated and phenolic acids are in the form of esters and, after their conversion to aglycons in our body, they are sulphated, glucuronidated or methylated [ 53 , 54].”
Background
Adsorption capacity of phenolic compounds onto cellulose and xylan
Costa, T. D. S., Rogez, H. L. G., & Pena, R. D. S. (2015) · Food Science and Technology · doi:10.1590/1678-457x.6568 · Cited by 40 · see citing works
“The consumption of certain foods may alter the bioavailability of PCs through their direct interaction with others food components, such as proteins and polysaccharides (Manach et al., 2004; Silberberg et al., 2006; D’Archivio et al., 2010).”
Background
Oral Pharmacokinetics of Hydroxycinnamic Acids: An Updated Review
Veras, K. S., Fachel, F. N. S., de Araújo, B. V., Teixeira, H. F., & Koester, L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122663 · Cited by 39 · see citing works
“Comparing these results with those reported previously indicates that the absorption of FA is higher in the intestine than in the stomach, and the intestine is the first site of metabolism, followed by the liver [68,140,144].”
BackgroundResult
Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656
Scholz, E. P., Zitron, E., Kiesecker, C., Thomas, D., Kathöfer, S., Kreuzer, J., Bauer, A., Katus, H. A., Remppis, A. B., Karle, C. A., et al. (2006) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2006.06.002 · Cited by 39 · see citing works
Cashew gum and maltrodextrin particles for green tea ( Camellia sinensis var A ssamica ) extract encapsulation
Silva, F. J. D. C., Torres, L. B. D. V., Silva, L., de Figueiredo, R. W., Garruti, D. D. S., de Araújo, T. G., Duarte, A. S. G., de Brito, D. H. A., & Ricardo, N. M. P. S. (2018) · Food Chemistry · doi:10.1016/j.foodchem.2018.04.028 · Cited by 38 · see citing works
“It is possible to determine the potential to be exploited in the dry green tea extract as a source of compounds of interest (Silberberg et al., 2006).”
Background
Physiologically based kinetic modeling of hesperidin metabolism and its use to predict in vivo effective doses in humans
Boonpawa, R., Spenkelink, A., Punt, A., & Rietjens, I. M. C. M. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600894 · Cited by 37 · see citing works
Effects of Polyphenols from Grape Seeds on Renal Lithiasis
Grases, F., Prieto, R., Fernandez-Cabot, R. A., Costa‐Bauzá, A., Tur, F., & Torres, J. J. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/813737 · Cited by 36 · see citing works
“Polyphenols were administered in drinking water because their bioavailability can improve compared to administration by a single daily dose [20, 21].”
Background
Complexation with β-cyclodextrin confers oral activity on the flavonoid dioclein
Rezende, B. A., Côrtes, S. F., Sousa, F. B. D., Lula, I. S., Schmitt, M., Sinisterra, R. D., & Lemos, V. S. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.09.046 · Cited by 36 · see citing works
Extraction and bioconversion of kaempferol metabolites from cauliflower outer leaves through fungal fermentation
Huynh, N. T., Smagghe, G. J., Gonzales, G. B., Camp, J. V., & Raes, K. (2015) · Biochemical Engineering Journal · doi:10.1016/j.bej.2015.12.005 · Cited by 36 · see citing works
Early-life supplementation of grape polyphenol extract promotes polyphenol absorption and modulates the intestinal microbiota in association with the increase in mRNA expression of the key intestinal barrier genes
Lu, F. L., Li, Y., Zhou, B., Guo, Q. Q., & Zhang, Y. (2020) · Food & Function · doi:10.1039/d0fo02231d · Cited by 36 · see citing works
Changes in phytochemical composition, bioactivity and in vitro digestibility of guayusa leaves (Ilex guayusa Loes.) in different ripening stages
Villacís‐Chiriboga, J., García‐Ruiz, A., Baenas, N., Moreno, D. A., Meléndez‐Martínez, A. J., Stinco, C. M., Jerves‐Andrade, L., León-Tamaríz, F., Ortiz‐Ulloa, J., & Ruales, J. (2017) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.8675 · Cited by 34 · see citing works
Effect of the Plant Matrix on the Uptake of Luteolin Derivatives-containing Artemisia afra Aqueous-extract in Caco-2 cells
Mukinda, J. T., Syce, J. A., Fisher, D., & Meyer, M. (2010) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2010.05.058 · Cited by 31 · see citing works
Effects of Caffeic Acid and Quercetin on In Vitro Permeability, Metabolism and In Vivo Pharmacokinetics of Melatonin in Rats: Potential for Herb-Drug Interaction
Jana, S., & Rastogi, H. (2017) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-016-0393-7 · Cited by 30 · see citing works
“Poly phenols (caffeic acid and quercetin) present in many fruits and vegetables [32].”
Background
Delivery of Flavonoids and Saponins from Black Bean (Phaseolus vulgaris) Seed Coats Incorporated into Whole Wheat Bread
Chávez-Santoscoy, R. A., Lazo‐Vélez, M. A., Serna-Saldivar, S. O., & Gutierrez-Uribe, J. A. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020222 · Cited by 30 · see citing works
“Interestingly, it has been reported that the combination of different polyphenols improved bioavailability, besides presenting a synergistic effect on their bioactivity [57,58].”
Background
In vitro simulated digestion on the biostability of Hibiscus cannabinus L. seed extract
Wong, Y. H., Tan, C. P., Long, K., & Nyam, K. L. (2014) · Czech Journal of Food Sciences · doi:10.17221/222/2013-cjfs · Cited by 28 · see citing works
“Bioavailability of polyphenols to peripheral tissues can be diminished by high intestinal and biliary secretion of their conjugates (Silberberg et al. 2006).”
Background
Microencapsulation of green tea extract (Camellia sinensis var assamica) to increase the bioaccessibility of bioactive compounds and gastroprotective effects
Silva, F. M. R., da Silva, L. M. R., Duarte, A. S. G., Monteiro, C. E. D. S., Campos, A. R., Holanda, D. K. R., de Lima, A. C. S., Sabino, L. B. D. S., & de Figueiredo, R. W. (2021) · Food Bioscience · doi:10.1016/j.fbio.2021.101190 · Cited by 25 · see citing works
Polyphenol Compounds as Antioxidants for Disease Prevention: Reactive Oxygen Species Scavenging, Enzyme Regulation, and Metal Chelation Mechanisms inE. coliand Human Cells
Wang, H. C., & Brumaghim, J. L. (2011) · ACS symposium series · doi:10.1021/bk-2011-1083.ch005 · Cited by 24 · see citing works
Fluorescent Carbon Dots as Cost-Effective and Facile Probes for Caffeic Acid Sensing via a Fluorescence Quenching Process
Sun, Q., Long, Y., Li, H., Pan, S., Yang, J., Liu, S., & Hu, X. (2018) · Journal of Fluorescence · doi:10.1007/s10895-018-2213-8 · Cited by 24 · see citing works
Thymol in the intestinal tract of broiler chickens after sustained administration of thyme essential oil in feed
Oceľová, V., Chizzola, R., Battelli, G., Pisarcikova, J., Faix, S., Gai, F., & Plachá, I. (2018) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.12995 · Cited by 24 · see citing works
Study of dietary polyphenols from natural herbal sources for providing protection against human degenerative disorders
Mukherjee, C., & Chakraborty, S. (2021) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2021.101956 · Cited by 24 · see citing works
Effect of replacing a synthetic antioxidant for natural extract of yerba mate (Ilex paraguariensis) on the physicochemical characteristics, sensory properties, and gastrointestinal digestion in vitro of burgers
Feihrmann, A. C., Coutinho, F. H., dos Santos, I. C., de Marins, A. R., de Campos, T. A. F., da Silva, N. M., Duarte, V. A., Matiucci, M. A., de Souza, M. L. R., & Gomes, R. G. (2022) · Food Chemistry Advances · doi:10.1016/j.focha.2022.100130 · Cited by 22 · see citing works
Effect of simultaneous consumption of soymilk and coffee on the urinary excretion of isoflavones, chlorogenic acids and metabolites in healthy adults
Felberg, I., Farah, A., Monteiro, M. C., Godoy, R. L. D. O., Pacheco, S., Calado, V. M. D. A., & Donangelo, C. M. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.09.059 · Cited by 20 · see citing works
The Strong Anti-Kinetoplastid Properties of Bee Propolis: Composition and Identification of the Active Agents and Their Biochemical Targets
Ebiloma, G. U., Ichôron, N., Siheri, W., Watson, D. G., Igoli, J. O., & de Koning, H. P. (2020) · Molecules · doi:10.3390/molecules25215155 · Cited by 20 · see citing works
Saccharomyces cerevisiae biosorbed with grape pomace flavonoids: adsorption studies and in vitro simulated gastrointestinal digestion
de Oliveira, A. L. M. S., Maciel, G. M., Rossetto, R., de Liz, M. V., Ribeiro, V. R., & Haminiuk, C. W. I. (2019) · International Journal of Food Science & Technology · doi:10.1111/ijfs.14110 · Cited by 19 · see citing works
Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) Controls Efflux Transport of Hesperetin Sulfates in Sulfotransferase 1A3–Overexpressing Human Embryonic Kidney 293 Cells
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“One of the main causes for the poor absorption of hesperetin is extensive phase II metabolism (i.e., glucuronidation and sulfonation) in the intestine and liver (Silberberg et al., 2006; Takumi et al., 2012).”
Background
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van der Pijl, P. C., Foltz, M., Glube, N. D., Peters, S., & Duchateau, G. S. M. J. E. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.06.020 · Cited by 18 · see citing works
Health-Promoting Effects of Wine Phenolics
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The splanchnic metabolism of flavonoids highly differed according to the nature of the compound
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Metabolism of Flavonoids via Enteric Recycling: Role of Intestinal Disposition
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Influence of Dietary Antioxidants on Polyphenol Intestinal Absorption and Metabolism in Rats
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Authors: Silberberg, M., Morand, C., Mathevon, T., Besson, C., Manach, C., Scalbert, A., & Remesy, C.
Affiliations: Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
Corresponding author: Morand, C.
ORCID: Silberberg, M.
Morand, C.
Manach, C.
Scalbert, A.
Venue: European Journal of Nutrition
Publisher: Springer Science and Business Media LLC
Published: 2005-06-30
Volume: 45
Issue: 2
Pages: 88-96
ISSN: 1436-6207 (ISSN-L)
1436-6215
DOI: 10.1007/s00394-005-0568-5
OpenAlex: W1972077998
Cited by: 164
References: 37
Citations by year: 2026: 3 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 12 · 2016: 11 · 2015: 8 · 2014: 11 · 2013: 15 · 2012: 7
FWCI: 4.80
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: European Journal of Nutrition (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Keywords: polyphenol bioavailability, genistein, hesperetin, ferulic acid, bile secretion, enterohepatic circulation, flavonoids, intestinal absorption
MeSH terms: Animals, Bile Ducts, Biological Availability, Chromatography, High Pressure Liquid, Coumaric Acids, Dose-Response Relationship, Drug, Flavonoids, Hesperidin, Intestinal Absorption, Intestine, Small, Liver, Male, Perfusion, Phenols, Molecular Structure, Rats, Wistar, Genistein, Rats, Polyphenols

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The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites

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