ArticleThe AAPS journal2015
Triple Recycling Processes Impact Systemic and Local Bioavailability of Orally Administered Flavonoids.
Article in The AAPS journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 60 citations in OpenAlex.
- Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives.Journal of advanced research · 2025Review
- Oral targeting tilianin nanoplatform mitigates atherosclerosis through promoting macrophage phagocytosis and anti-inflammation.Materials today. Bio · 2025Article
- O-GlcNAcylated Hsp47 as a predictive biomarker in colorectal cancer: Kaempferol targets OGT-collagen axis for therapeutic intervention.International journal of biological sciences · 2025Article
- The Role of Genistein in Mammalian Reproduction.Molecules (Basel, Switzerland) · 2023Review
- Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules.Frontiers in pharmacology · 2023Article
- Review
- Pharmacokinetics of B-Ring Unsubstituted Flavones.Pharmaceutics · 2019Review
- Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease.Antioxidants (Basel, Switzerland) · 2019Review
- The roles of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated proteins (MRPs/ABCCs) in the excretion of cycloicaritin-3-O-glucoronide in UGT1A1-overexpressing HeLa cells.Chemico-biological interactions · 2018Article
- Pretreatment with Total Flavonoid Extract from Dracocephalum Moldavica L. Attenuates Ischemia Reperfusion-induced Apoptosis.Scientific reports · 2018Article
- Cellular Pharmacokinetic Model-Based Analysis of Genistein, Glyceollin, and MK-571 Effects on 5 (and 6)-Carboxy-2',7'-Dichloroflourescein Disposition in Caco-2 Cells.Journal of pharmaceutical sciences · 2018Article
- Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Regulate the Disposition of Acacetin Glucuronides.Pharmaceutical research · 2017Article
- Glucuronidation: driving factors and their impact on glucuronide disposition.Drug metabolism reviews · 2017Review
- In Vivo Exposure of Kaempferol Is Driven by Phase II Metabolic Enzymes and Efflux Transporters.The AAPS journal · 2016Article
- Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides.Molecular nutrition & food research · 2016Article
- Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for Metabolic and Transport Interactions.Journal of pharmaceutical sciences · 2016Article
- Genistein and Glyceollin Effects on ABCC2 (MRP2) and ABCG2 (BCRP) in Caco-2 Cells.International journal of environmental research and public health · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Triple recycling (i.e., enterohepatic, enteric and local recycling) plays a central role in governing the disposition of phenolics such as flavonoids, resulting in low systemic bioavailability but higher gut bioavailability and longer than expected apparent half-life. The present study aims to investigate the coexistence of these recycling schemes using model bioactive flavonoid tilianin and a four-site perfused rat intestinal model in the presence or absence of a lactase phlorizin hydrolase (LPH) inhibitor gluconolactone and/or a glucuronidase inhibitor saccharolactone. The result showed that tilianin could be metabolized into tilianin glucuronide, acacetin, and acacetin glucuronide, which are excreted into the bile and luminal perfusate (highest in the duodenum and lowest in the colon). Gluconolactone (20 mM) significantly reduced the absorption of tilianin and the enteric and biliary excretion of acacetin glucuronide. Saccharolactone (0.1 mM) alone or in combination of gluconolactone also remarkably reduced the biliary and intestinal excretion of acacetin glucuronide. Acacetin glucuronides from bile or perfusate were rapidly hydrolyzed by bacterial β-glucuronidases to acacetin, enabling enterohepatic and enteric recycling. Moreover, saccharolactone-sensitive tilianin disposition and glucuronide deconjugation, which was more active in the small intestine than the colon, points to the small intestinal origin of the deconjugation enzyme and supports the presence of local recycling scheme. In conclusion, our studies have demonstrated triple recycling of a bioactive phenolic (i.e., a model flavonoid), and this recycling may have an impact on the site and duration of polyphenols pharmacokinetics in vivo.
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