Absorption of andrographolides from Andrographis paniculata and its effect on CCl₄-induced oxidative stress in rats

Abstract

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42 ± 0.09 μg/ml and 1.31 ± 0.04 μg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl₄ administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl₄ did not showed significant alteration (p > 0.05) in plasma total antioxidant status (TAS) as compare to values of control group.

Introduction

Andrographis paniculata, Nees also known as “King of Bitters” from the family Acanthaceae is well known plant in Southeast Asia. Animal studies have shown that extracts of A. paniculata are biologically active. The leaf extracts of A. paniculata is a traditional remedy for treatment of infectious fever-causing diseases, colic pain, and loss of appetite, irregular stools and diarrhoea (Saxena et al., 1998). A. paniculata extract showed a protective effect against liver toxicity produce in mice by given them carbon tetrachloride, alcohol, or other toxic chemicals (Kapil et al., 1993).

The active components of A. paniculata are diterpene lactones found in the aerial parts of the plant. Total lactone and andrographolide are the common names used for the active chemical constituents (Deng et al., 1982). The main diterpenoid lactones that have been isolated from aerial parts of A. paniculata include andrographolide (AP, a bitter colourless crystal) and 14-deoxy-11,12-didehydroandrographolide (DIAP, needle crystal) (Matsuda et al., 1994) (Fig. 1). The andrographolides isolated from A. paniculata have been reported to possess protective effect against urothelial toxicity (Sheeja and Kuttan, 2006) and liver disorders including treatment of hepatitis (Sharma et al., 1992, Tang and Eisenbrandt, 1992, Holt et al., 1998).

Literature reports on analysis of diterpenoid lactones from A. paniculata in biological fluids focused on the separation of AP. To our knowledge, simultaneous determination of AP and DIAP in rat plasma after oral administration of A. paniculata extract for pharmacokinetic evaluation of A. paniculata preparations has not been reported. Therefore, the purpose of the present study was to determine plasma levels of AP and DIAP from A. paniculata in rats and effect of the extract on CCl₄-induced oxidative stress in rats.