Interaction of the Bioactive Flavonol, Icariin, with the Essential Human Solute Carrier Transporters

Li, Zhen; Cheung, Florence Shin Gee; Zheng, Jian‐Guo; Chan, Ting Fung; Zhu, Ling; Zhou, Fanfan

doi:10.1002/jbt.21540

Cited by 21 publications

(15 citation statements)

References 47 publications

(72 reference statements)

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“…[19]. We also showed Icariin, a natural prenylated flavonol glycoside popularly used to treat sexual dysfunction in males and osteoporosis remarkably impairs the substrate uptake via OATP1B1, OATP1B3 and OATP2B1, which observation is consistent with the early study [78,79].…”

Section: Organic Anion Transporting Peptides (Oatps)supporting

confidence: 87%

The Interactions of Herbal Compounds with Human Organic Anion/Cation Transporters

Xiao¹,

Chan²,

Xu³

et al. 2014

J Pharmacogenomics Pharmacoproteomics

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OATs are known to mediate uptake of water-soluble, negatively charged organic molecules with low molecular weight such as steroid hormones and their conjugates, biogenic amines, numerous drugs and toxins [6,7]. So far, there are nine human OAT isoforms identified with OAT1, OAT2, OAT3 and OAT4 better characterized [1,6]. Tissue distribution OAT1 was first discovered as a para-aminohippurate (PAH) transporter in 1997 [7-9], which is abundantly expressed at the basolateral membrane of renal proximal tubular cells [10-15]. OAT2 was found to be predominantly expressed in the liver and also located at the blood-facing membrane of renal tubular cells [16,17]. OAT3 is widely expressed in the kidney, brain and liver [18]. OAT4 distributes at the apical membrane of renal proximal tubular cells and the basolateral membrane of syncytiotrophoblasts in the placenta [12,19-22]. OAT5 and OAT7 are found in human liver, while OAT10 distributes at the apical membrane of renal proximal tubules cells [23-25].

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Section: Organic Anion Transporting Peptides (Oatps)supporting

confidence: 87%

The Interactions of Herbal Compounds with Human Organic Anion/Cation Transporters

Xiao¹,

Chan²,

Xu³

et al. 2014

J Pharmacogenomics Pharmacoproteomics

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“…Inhibition or stimulation of OATP2B1's function by drugs or foods could alter the pharmacokinetics of OATP2B1 substrates and potentially lead to adverse effects. Quite a few interactions between OATP2B1 and natural products have been reported in the literature (Fuchikami et al, 2006;Imanaga et al, 2011;Kock et al, 2013;Li et al, 2014;Mandery et al, 2010;Satoh et al, 2005;Shirasaka et al, 2013a,b;Tapaninen et al, 2010Tapaninen et al, , 2011Roth et al, 2011), suggesting that OATP2B1 could interact with a wide range of natural products. To identify more OATP2B1 modulators from natural products and to avoid potential adverse drug-drug and drug-food interactions, in this work the effects of 27 natural compounds and extracts on the function of OATP2B1 have been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Roth et al (2011) reported that green tea catechins epicatechin gallate and epigallocatechin gallate significantly inhibited OATP2B1-mediated E3S uptake. Several flavonoids, silymarin flavonolignans, and antidiabetic drugs have also been reported to inhibit OATP2B1 in vitro (Bachmakov et al, 2008;Klatt et al, 2013;Kock et al, 2013;Li et al, 2014;Mandery et al, 2010). These reports demonstrated that OATP2B1 could interact with a wide range of natural products.…”

Section: Introductionmentioning

confidence: 92%

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Wen

Shi

Bian

et al. 2015

Pharmaceutical Biology

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Context: Organic anion-transporting polypeptide 2B1 (OATP2B1) which is highly expressed in enterocytes and hepatocytes could be a key determinant for the intestinal absorption and hepatic uptake of its substrate drugs. Natural products are commonly used in traditional Chinese medicine, foods, and beverages. Objective: The objective of this study is to determine the OATP2B1-mediated drug interactions that could occur between natural products and OATP2B1 substrate drugs. Materials and methods: Human OATP2B1 was transiently expressed in human embryonic kidney (HEK293) cells and characterized by immunofluorescence, Western blot, and uptake assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting OATP2B1 substrates estrone-3-sulfate (E3S) and three statins had been developed and were employed to investigate the effects of 27 frequently used natural products on the function of OATP2B1. Uptake of 5 lM E3S and 1 lM statins in the absence or presence of natural products was measured at 37 C for 2 min with empty vector-and OATP2B1-transfected HEK293 cells. The IC 50 values of inhibitors for OATP2B1-mediated 5 lM E3S uptake were determined. Results: Our results showed that mulberrin, scutellarin, quercetin, and glycyrrhetinic acid were strong inhibitors of OATP2B1-mediate E3S uptake with IC 50 values being 1.8, 2.0, 7.5, and 13.0 lM, which were comparable with their plasma concentrations in clinical trials. They also inhibited OATP-mediated uptake of atorvastatin, fluvastatin, and rosuvastatin. These results indicated that clinically relevant drug interactions could occur between these natural compounds and OATP2B1 substrate drugs. Discussion and conclusion: The information obtained from this study might be helpful to predict and to avoid potential OATP2B1-mediated drug interactions.

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“…In vivo, scutellarin is highly distributed in hepatocytes, the same as the main target cells of HMG-GoA reductase statins 7 . Many Traditional Chinese Medicines (TCMs) active substances have significant effects on substrates of hepatic transporter and impact transport efficiency [8][9][10] . Transporters play a key role in drug pharmacokinetics and the competition for them is vital for drug uptake, distribution, and elimination 11,12 .…”

Section: Scutellarin Inhibition Of the Rosuvastatin Uptake In Rat Hepmentioning

confidence: 99%

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

Liu

Guo²,

Liu³

et al. 2020

Sci Rep

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www.nature.com/scientificreports www.nature.com/scientificreports/ by hepatocytes 13 . However, the mechanism of OATP1B1 involvement remains unclear, or whether scutellarin and rosuvastatin compete for OATP1B1. Therefore, in this study, we treated rats with rosuvastatin alone, or with a combination of rosuvastatin and a series concentration of scutellarin, to examine the plasma and hepatic levels of rosuvastatin in rats, as well as in OATP1B1 transfected HEK293T cells. Materials and MethodsAnimals. A total of 48 healthy male Sprague-Dawley rats weighing 230-270 g were obtained by the Experimental Animal Center of Nanchang University Medical College. Animals were housed in individual cages in an air-conditioned room at room temperature of 25 ± 1 °C with a 12 h light: 12 h dark period. The study was approved by the Ethical Committee of JiangXi Medical College, and all experiments were carried out with humane care according the Animal Care and Use Committee (ACUC) of Nanchang University Medical College. Rats were given free access to drinking water, after experiments, rats were euthanized by intraperitoneal injection of sodium pentobarbital with a dose of 200 mg/kg. Treatment and sampling. The rats were randomly divided into two groups with 24 rats in each group: the rosuvastatin group (rosuvastatin 10 mg/kg) and the combination treatment group (rosuvastatin 10 mg/kg + scutellarin 50 mg/kg), the concentrations used in the animal were transformed from clinical dose. The treatment was administered by gavage in the morning before feeding, and scutellarin was administered immediately following the rosuvastatin administration for the combination treatment group. In each group, 6 rats were maintained throughout the study and used for orbital vein blood sampling (0.15 ml) at 0 (before), 0.5, 1.0, 1.5, 2.0, 3.0, 5.0, 8.0, 12.0, 18.0, 24.0 h post treatment, to obtain the concentration-time profile data. Six of the remaining rats in each group were sacrificed at 1 h, 2 h, and 6 h post treatment (each time point) to sample the 0.5 ml of eyeball blood and the liver tissues. Blood was stored in heparinized tubes and the plasma was separated by centrifugation, then stored at −80 °C for further analysis. Scientific RepoRtS |(2020) 10:1308 | https://doi.

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Interaction of the Bioactive Flavonol, Icariin, with the Essential Human Solute Carrier Transporters

Cited by 21 publications

References 47 publications

The Interactions of Herbal Compounds with Human Organic Anion/Cation Transporters

The Interactions of Herbal Compounds with Human Organic Anion/Cation Transporters

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

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