Evidence map›Paper›PMID 32918091›Full record

ArticleArchives of toxicology2020

Rapid intestinal glucuronidation and hepatic glucuronide recycling contributes significantly to the enterohepatic circulation of icaritin and its glucuronides in vivo.

Yi Rong, Yifan Tu, Taijun Yin, Zhiyun Meng, Guifang Dou, Ming Hu

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Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Journal of pharmaceutical analysis · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Yi RongDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.ORCID http://orcid.org/0000-0002-1053-2700
Yifan TuDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA.
Taijun YinDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA.
Zhiyun MengDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
Guifang DouDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China. dougf@bmi.ac.cn.
Ming HuDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA. mhu@uh.edu.
University of Houston · USCapital Medical University · CNNational Institutes of Pharmaceutical Research and Development (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Icaritin (ICT), a prenylflavonoid derivative extracted from the Epimedium genus, has exhibited antitumor effects in hepatocellular carcinoma (HCC) cells and safety and tolerance in clinical settings. However, ICT exhibits low blood concentration and the in vivo dominant plasma species of ICT is glucuronides [icaritin-3-glucuronide (G1), icaritin-7-glucuronide (G2) and icaritin-3, 7-diglucuronide (DIG)]. Therefore, how ICT reaches the liver and exerts its effect with low toxicity remains unknown. Therefore, pharmacokinetic experiments (p.o. 5 mg/kg with/out 50 mg/kg inhibitor combo), intestinal perfusion (2 μM ICT), portal vein infusion (1.6 μM ICT, 7.1 μM G1, 6.8 μM G2 and 4.4 μM DIG), and in vitro studies (the concentration range of substrates: 0.3-10 μM) were conducted in the present study. Ultimately, ICT was shown to undergo glucuronidation by the intestine and subsequent uptake by hepatocytes via organic anion transporting peptides (OATPs) as conjugates, followed by biliary excretion mainly as diglucuronide. In conclusion, we found for the first time that the intestine is considered as the major metabolic organ, liver as the main recycling organ for the enterohepatic recycling (EHR) of ICT. Moreover, DIG is the main species in the systemic circulation following oral administration of ICT which explains the low toxicity of ICT in clinical settings.

Indexed as

AnimalsCaco-2 CellsChromatography, High Pressure LiquidEnterohepatic CirculationFlavonoidsGlucuronidesHEK293 CellsHepatobiliary EliminationHepatocytesHumansIntestinesLiverMaleMicrosomes, LiverOrganic Anion TransportersPerfusionFlavonoidsGlucuronidesicaritinOrganic Anion TransportersDiglucuronidationEnterohepatic recycling (EHR)Hepatocellular carcinoma (HCC)Icaritin

Identifiers

PMID32918091
OpenAlexW3085683533

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.