Andrographis paniculataExtract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats

Haw-Wen Chen,Cheng-Tzu Liu,Chin-Shiu Huang,Chong-Kuei Lii,Chiung-Tong Chen,Jia-Rong Chiang,Hsien-Tsung Yao,Pei-Fen Liu,Chien-Chun Li

doi:10.1155/2013/982689

Abstract

Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE) and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0–12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.

Highlights

Andrographis paniculata (Burm. f) is a medicinal herb cultivated in Southeast Asia
Animal studies have indicated that the aqueous extract of A. paniculata, the ethanolic extract of A. paniculata (APE), and andrographolide lower blood glucose levels and induce glucose transporter 4 activity in streptozotocin-induced diabetic rats [11,12,13]
We investigated the modulatory potency of A. paniculata extract (APE) and andrographolide on the expression and activity of Cytochrome P450 (CYP) isozymes, glutathione S-transferases (GST), Uridine diphosphateglucuronosyltransferases (UGT), and P-glycoprotein in rat liver

Summary

Introduction

F) is a medicinal herb cultivated in Southeast Asia. It is widely used as a traditional medicine in Taiwan, China, India, and Thailand for the treatment of infections, cold, fever, inflammation, and diarrhea [1]. Andrographolide is the major diterpene lactone of A. paniculata and accounts for 1.7% and 0.8% of the weight of dried leaves and stems of the herb, respectively [2]. A. paniculata and andrographolide have recently attracted considerable interest because of their diverse physiological functions and therapeutic potential, including antioxidant [3], anti-inflammatory [4], antiapoptosis [5], antiatherosclerosis [6], anticancer [7], antivirus [8], and hypoglycemia effects [9].

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