Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies

Yuan, Zhongwen; Li, Yazhuo; Liu, Zhongqiu; Feng, Senling; Zhou, Hua; Liu, Changxiao; Liu, Liang; Xie, Yu

doi:10.1016/j.phrs.2017.09.019

Cited by 44 publications

(53 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Baicalein was selected based on primary screening experiments in Caco-2 cells. The mean efflux ratios of silybin A and B in Caco-2 model were 5.62 and 5.13, respectively, indicating active transport of efflux, which is consistent with the literature ( Yuan et al, 2017 ). As shown in Figures 1A – C , baicalein could inhibit efflux transport of silybin (10 μM) in the Caco-2 cell monolayers with the lowest effective dosage at 0.5 μM.…”

Section: Resultssupporting

confidence: 91%

“…Understanding the interactions between efflux transporter(s) and baicalein could help to illustrate the drug-drug interaction mechanism as silybin is a substrate of both MRP2 and BCRP ( Yuan et al, 2017 ). Transport experiments were conducted across transfected MDCK-II (MDCKII-MDR1, MDCKII-MRP2, and MDCKII-BCRP) cell lines, which were recommended as in vitro models for the determination of the extent of transporter inhibition ( Agarwal et al, 2007 ; Giacomini et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

“…Wild type MDCK II, MDR1-MDCK II, BCRP-MDCK II, and MRP2-MDCK II cells were kindly supplied by the Netherlands Cancer Institute (Amsterdam, Netherlands). Transport study was carried out with Caco-2 cells, and MDCK II cells were transfected using a previously established method with slight modifications ( Yuan et al, 2017 ). The Caco-2 cells were cultured at 37°C/5% CO 2 in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum, 1% nonessential amino acids, and 1% penicillin-streptomycin.…”

Section: Methodsmentioning

confidence: 99%

“…Substrates or inhibitors of these transporters can limit the transport of other molecules, which potentially affect the bioavailability, distribution, and/or elimination by competing for transport ( Marquez and Van Bambeke, 2011 ; Konig et al, 2013 ; Gupta et al, 2015 ). We have demonstrated that silybin is a substrate of the efflux transporters breast cancer resistance protein (BCRP, gene symbol ABCG2) and multi-drug resistance protein 2 (MRP2, gene symbol ABCC2) ( Yuan et al, 2017 ). In this study, we wanted to enhance the bioavailability and pharmacodynamic effects of silybin via the inhibition of the efflux transporters BCRP and MRP2 by using baicalein, which was selected based on the primary screening results in our laboratory.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2

Peng

Zhou

et al. 2018

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Although hepatoprotective properties of silybin are well documented, the clinical therapeutic efficacy is limited by its low bioavailability due to absorption rates, extensive phase II metabolism, and biliary excretion. As our previous study indicated that metabolic enzymes may have limited effects on the pharmacokinetic (PK) behavior of silymarin, here, we intended to increase the oral bioavailability and bio-efficacy of silybin through the inhibition of active efflux. In Caco-2 and transfected MDCKII cell models, flavone baicalein significantly inhibited the efflux of silybin as a BCRP and MRP2 inhibitor. In addition, baicalein reduced the biliary excretion index (BEI) and biliary clearance of silybin conjugates in the sandwich-cultured rat hepatocyte (SCH) model, indicating the inhibition of baicalein in biliary excretion of conjugated silybin metabolites. PK study demonstrated that baicalein significantly increased the area under the curve (AUC) and Cmax of silybin and its conjugates, suggesting enhanced absorption in vivo. Moreover, coadministration of silybin with baicalein boosted the liver protective, antioxidant, and anti-inflammatory effects of silybin in the carbon tetrachloride (CCl4)-induced liver injury model in comparison with silybin given alone. In summary, efflux transporters play a critical role in the low bioavailability of silybin, while inhibition of breast cancer resistance protein (BCRP) and multi-drug resistance protein 2 (MRP2) by baicalein can significantly increase the absorption and bio-efficacy of silybin, which provides a new combination therapeutic approach for the treatment of chronic liver diseases.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2

Peng

Zhou

et al. 2018

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the experiments, all chemicals were prepared immediately before treatment; CCl 4 was dissolved in paraffin oil, whereas KCZ was dispersed in 0.6% sodium carboxymethyl cellulose (CMC-Na). The dosage of CCl 4 and KCZ was established according to previous experiments (Yuan et al, 2018;Minamiyama et al, 2004).…”

Section: Chemicals and Their Preparationmentioning

confidence: 99%

Ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats by suppressing inflammation and oxidative stress

Zhou¹,

Peng²,

Zhou³

et al. 2019

J. Toxicol. Sci.

View full text Add to dashboard Cite

Several studies have demonstrated the chemopreventive role of ketoconazole in animal models of liver injury. However, the underlying molecular mechanisms of this hepatoprotective effect are poorly understood. The present study assessed the potential of ketoconazole to enhance resistance to carbon tetrachloride-induced hepatotoxicity in vivo in a rat model. Ketoconazole pretreatment adult male rats were intraperitoneally injected with carbon tetrachloride for 24 hr and various hepatic parameters were analyzed. We observed decreased serum transaminases activity, reduced nuclear RelA/p65 expression, and suppressed production of pro-inflammatory cytokines in the liver tissue. Histopathological examination demonstrated ketoconazole pretreatment to extensively prevent liver injury. In addition, it significantly increased nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) protein expression, glutathione (GSH) to oxidized glutathione (GSSG) ratio, and antioxidant enzymes gene expression. These results suggest that ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats, signifying its anti-inflammatory and antioxidant functions.

show abstract

Excretion of Drugs and Their Metabolites into the Bile

Gao,

Etim,

Sunsong

et al. 2023

Oral Bioavailability and Drug Delivery

View full text Add to dashboard Cite

Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies

Cited by 44 publications

References 35 publications

Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2

Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2

Ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats by suppressing inflammation and oxidative stress

Excretion of Drugs and Their Metabolites into the Bile

Contact Info

Product

Resources

About