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Open AccessArticle

Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins

by Haoyue Zhang 1,2,†, Xueping Wang 1,†, Ting Wang 3, Kaixian Chen 1,3, Heyao Wang 3,*, Qi Jia 1,* and Yiming Li 1,*
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2018, 23(12), 3318;
Received: 29 November 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
This study investigated the possible enhancement of berberine’s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db 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–tandem mass spectrometry (LC–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 db/db 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. View Full-Text
Keywords: oligomeric proanthocyanidins; P-glycoprotein; hypoglycemic effect; berberine; pharmacokinetics oligomeric proanthocyanidins; P-glycoprotein; hypoglycemic effect; berberine; pharmacokinetics
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Zhang, H.; Wang, X.; Wang, T.; Chen, K.; Wang, H.; Jia, Q.; Li, Y. Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins. Molecules 2018, 23, 3318.

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