Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins

This study investigated the possible enhancement of berberine&#8217;s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic <i>db</i>/<i>db</i> mice. The...

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Main Authors: Haoyue Zhang, Xueping Wang, Ting Wang, Kaixian Chen, Heyao Wang, Qi Jia, Yiming Li
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/23/12/3318
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author Haoyue Zhang
Xueping Wang
Ting Wang
Kaixian Chen
Heyao Wang
Qi Jia
Yiming Li
author_facet Haoyue Zhang
Xueping Wang
Ting Wang
Kaixian Chen
Heyao Wang
Qi Jia
Yiming Li
author_sort Haoyue Zhang
collection DOAJ
description This study investigated the possible enhancement of berberine&#8217;s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic <i>db</i>/<i>db</i> mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography&#8315;tandem mass spectrometry (LC&#8315;MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic <i>db</i>/<i>db</i> mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.
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spelling doaj.art-abe2c74d2ef546a7878a5ad31cb622a02022-12-21T19:39:57ZengMDPI AGMolecules1420-30492018-12-012312331810.3390/molecules23123318molecules23123318Enhancement of Berberine Hypoglycemic Activity by Oligomeric ProanthocyanidinsHaoyue Zhang0Xueping Wang1Ting Wang2Kaixian Chen3Heyao Wang4Qi Jia5Yiming Li6School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, ChinaThis study investigated the possible enhancement of berberine&#8217;s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic <i>db</i>/<i>db</i> mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography&#8315;tandem mass spectrometry (LC&#8315;MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic <i>db</i>/<i>db</i> mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.https://www.mdpi.com/1420-3049/23/12/3318oligomeric proanthocyanidinsP-glycoproteinhypoglycemic effectberberinepharmacokinetics
spellingShingle Haoyue Zhang
Xueping Wang
Ting Wang
Kaixian Chen
Heyao Wang
Qi Jia
Yiming Li
Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
Molecules
oligomeric proanthocyanidins
P-glycoprotein
hypoglycemic effect
berberine
pharmacokinetics
title Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
title_full Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
title_fullStr Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
title_full_unstemmed Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
title_short Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins
title_sort enhancement of berberine hypoglycemic activity by oligomeric proanthocyanidins
topic oligomeric proanthocyanidins
P-glycoprotein
hypoglycemic effect
berberine
pharmacokinetics
url https://www.mdpi.com/1420-3049/23/12/3318
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AT kaixianchen enhancementofberberinehypoglycemicactivitybyoligomericproanthocyanidins
AT heyaowang enhancementofberberinehypoglycemicactivitybyoligomericproanthocyanidins
AT qijia enhancementofberberinehypoglycemicactivitybyoligomericproanthocyanidins
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