Planta Med 2010; 76(9): 876-881
DOI: 10.1055/s-0029-1240815
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Increased Plasma Exposures of Five Protoberberine Alkaloids from Coptidis Rhizoma in Streptozotocin-Induced Diabetic Rats: Is P‐GP Involved?

Sen Yu2 , Yunli Yu1 , Li Liu1 , Xinting Wang1 , Shousi Lu1 , Yan Liang1 , Xiaodong Liu1 , Lin Xie1 , Guangji Wang1
  • 1Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China
  • 2Jiangsu Simcere Pharmaceutical R & D Co., Ltd., Nanjing, P. R. China
Further Information

Publication History

received Sept. 15, 2009 revised Dec. 22, 2009

accepted Dec. 28, 2009

Publication Date:
27 January 2010 (online)

Abstract

Our previous study showed a higher exposure of berberine, palmatine, coptisine, epiberberine and jatrorrhizine in 6-week streptozotocin (STZ)-induced diabetic rats, after oral administration of Coptidis Rhizoma extract. The aim of the present study was to investigate whether the function and expression of intestinal P-glycoprotein (P‐GP) was downregulated in STZ-induced diabetic rats and if the impairment of P‐GP function and expression contributed to the exposure increase of the five protoberberine alkaloids. Plasma concentration-time profiles of the drugs in the portal vein were obtained after oral administration of Coptidis Rhizoma extract. The effective permeability of the drug across duodenum and ileum were measured using in situ single-pass intestine perfusion. P‐GP function in the rat intestine was assessed by measuring the absorption of rhodamine 123 (Rho123). P‐GP levels were evaluated using Western blots. It was found that the Cmax and AUC0-8 values of five alkaloids in the portal vein of diabetic rats were significantly higher than those in the control rats. Diabetic rats also exhibitd a higher level of Rho123 in the portal vein, which showed impairment of P‐GP function. A higher effective permeability of the tested drug was found in the duodenum of diabetic rats using in situ single-pass intestine perfusion, indicating that berberine and Rho123 transported more easily across the intestinal barrier of diabetic rats. A lower level of P‐GP protein was found in the duodenum, jejunum and ileum of the diabetic rats as compared with age-matched control rats. All these results suggested that the function and expression of P‐GP were impaired in the intestine of STZ-induced diabetic rats which, at least partly, contributed to the exposure increase of the five protoberberine alkaloids.

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Prof. Dr. Xiaodong Liu

Key Laboratory of Drug Metabolism and Pharmacokinetics
China Pharmaceutical University

24 Tongjia Xiang

210009 Nanjing

People's Republic of China

Phone: + 86 25 83 27 10 06

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Email: xdliu@cpu.edu.cn

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