Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux

Shan, Yongqiang; Ren, Gang; Wang, Yanxiang; Pang, Jing; Zhao, Zhiyun; Yao, Jing; You, Xuefu; Si, Shuyi; Song, Dan–Qing; Kong, Weijia; Jiang, Jian‐Dong

doi:10.1016/j.metabol.2012.09.009

Cited by 47 publications

(38 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After removal of chemicals, Caco-2 cells treated with Tet pumped 46.5% of BBR out of cells in 3 h, which was greatly lower than that of BBR alone (74.6%, p<0.05) and was agree with our previous report. 24) As a result, in the presence of Tet, the remained BBR in Caco-2 cells after 3 h' efflux increased about 3.6 times compared to that without Tet (p<0.001). These results implied that Tet may improve the intestinal absorption of BBR.…”

Section: Tet Overcomes P-gp Efflux and Decreases P-gp Expression In Cmentioning

confidence: 84%

“…23) Overcoming P-gp efflux is a strategy to improve the absorption and pharmacokinetics of BBR. In our previous work, 24) we have identified a BBR analogue with decreased affinity to P-gp and had improved hypoglycemic efficacy in diabetic mice. In this study, we used another strategy targeting P-gp to improve the intestinal absorption and hypoglycemic efficacy of BBR.…”

Section: )mentioning

confidence: 99%

“…Harvested cells were then re-suspended in 100 µL of PBS; 50 µL of which was used for protein extraction and quantification, another 50 µL was mixed with 150 µL of acetonitrile (Sigma-Aldrich Co., St. Louis, MO, U.S.A.) for extraction and assay of BBR concentration, which was determined by LC-MS/MS as described previously. 24,30) The intracellular BBR concentrations were normalized to protein contents and presented as µmol/g protein.…”

Section: Cellmentioning

confidence: 99%

“…Plasma concentrations of BBR were determined by LC-MS/MS as described previously. 24,30) Glucose Consumption Assay HepG2 cells were treated with BBR (with or without Tet) or Tet as indicated. After incubation for 24 h, cultured media were collected and centrifuged at 1200 rpm for 5 min.…”

Section: Cellmentioning

confidence: 99%

“…[16][17][18] Our previous study proved that Tet could inhibit the efflux of BBR greatly in Caco-2 cells. 24) To learn if Tet had any influence on the uptake of BBR, Caco-2 cells were treated with BBR (with or without Tet) for 3 h, intracellular concentration of BBR was determined with LC-MS/MS. As shown in Fig.…”

Section: Tet Overcomes P-gp Efflux and Decreases P-gp Expression In Cmentioning

confidence: 99%

See 4 more Smart Citations

Tetrandrine Potentiates the Hypoglycemic Efficacy of Berberine by Inhibiting P-Glycoprotein Function

Shan

Zhu

Pang

et al. 2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

This study was designed to improve the absorption and hypoglycemic efficacy of berberine (BBR), which is a substrate of P-glycoprotein (P-gp), by combination with a P-gp inhibitor tetrandrine (Tet). Flow cytometry and LC-MS/MS were used to determine the cellular efflux or retention of chemicals. Pharmacokinetic study was performed in ICR mice following oral administration of the study compounds. The hypoglycemic efficacies of the compounds were evaluated in diabetic KK-Ay mice. In the in vitro experiments, Tet significantly inhibited the efflux and increased the uptake of P-gp substrates rhodamine-123 as well as BBR in MCF7/DOX cells and Caco-2 intestinal cells. Meanwhile, Tet greatly reduced the expression of P-gp in Caco-2 cells. The inhibition of BBR efflux by Tet was translated into improved pharmacokinetics in vivo. When co-administered, Tet dose-dependently increased the average maximum concentration (C max ) and area under concentration-time curve (AUC 0-24 ) of BBR in mice. Tet itself had no impact on glucose metabolism. However, it greatly potentiated the hypoglycemic efficacy of BBR in diabetic KK-Ay mice. In addition, we found that Tet had moderate inhibitory effect on the catalytic activity of CYP3A4, which played a role in the bio-transformation of BBR, and this may also take part in the improvement of the pharmacokinetics of BBR. In summary, combination with P-gp inhibitors such as Tet can improve the pharmacokinetics and hypoglycemic efficacy of BBR greatly; this implicates a feasible strategy for exploring the therapeutic effects of BBR and other pharmaceuticals which are substrates of P-gp.

show abstract

Section: Tet Overcomes P-gp Efflux and Decreases P-gp Expression In Cmentioning

confidence: 84%

Section: )mentioning

confidence: 99%

Section: Cellmentioning

confidence: 99%

Section: Cellmentioning

confidence: 99%

Section: Tet Overcomes P-gp Efflux and Decreases P-gp Expression In Cmentioning

confidence: 99%

See 3 more Smart Citations

Tetrandrine Potentiates the Hypoglycemic Efficacy of Berberine by Inhibiting P-Glycoprotein Function

Shan

Zhu

Pang

et al. 2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

Development and application of a UPLC‐MS/MS method for simultaneous determination of fenofibric acid and berberine in rat plasma: application to the drug–drug pharmacokinetic interaction study of fenofibrate combined with berberine after oral administration in rats

Yang

Liu

et al. 2016

Biomedical Chromatography

View full text Add to dashboard Cite

With the purpose of carrying out pharmacokinetic interaction studies ofnberberine (BBR) and fenofibrate (FBT), an UPLC-MS/MS method has been developed and validated. The analytes, BBR and fenofibric acid (FBA, metabolite of FBT) and the internal standard, tetrahydropalmatine, were extracted with dichloromethane-diethyl ether (3:2, v/v) and separated on an Agilent Eclipse XDB C 18 column using a mobile phase composed of acetonitrile and water. With positive ion electrospray ionization, the analytes were monitored on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. Linear calibration curves were obtained over the concentration ranges of 0.1-100.0 ng/mL for BBR and 10.0-50,000.0 ng/mL for FBA. For BBR and FBA, the intra-and inter-day precisions were <11.5 and 11.9%, respectively. The accuracy was within 11.7% and 11.3%. The mean recoveries of BBR at three concentrations of 0.2, 20.0, 80.0 ng/mL were >85.6%, and those of FBA at three concentrations of 20.0, 2500.0, 40,000.0 ng/mL were >87.9%. Consequently, the proposed method was applied to the pharmacokinetic interaction study of FBT combined with BBR after oral administration in rats and was proved to be sensitive, specific and reliable to analyze BBR and FBA in biological samples simultaneously.

show abstract

Research progress on pharmacological effects and bioavailability of berberine

Cui,

Zhou,

Jin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux

Cited by 47 publications

References 47 publications

Tetrandrine Potentiates the Hypoglycemic Efficacy of Berberine by Inhibiting P-Glycoprotein Function

Tetrandrine Potentiates the Hypoglycemic Efficacy of Berberine by Inhibiting P-Glycoprotein Function

Development and application of a UPLC‐MS/MS method for simultaneous determination of fenofibric acid and berberine in rat plasma: application to the drug–drug pharmacokinetic interaction study of fenofibrate combined with berberine after oral administration in rats

Research progress on pharmacological effects and bioavailability of berberine

Contact Info

Product

Resources

About