Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats

Abstract

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.

Fig. 1

Plasma BBR concentration–time profile after intravenous (iv) and oral administration of BBR along (control) and in combination with TPGS (test) in rats. Data are shown as mean concentration, and error bars represent SD (n = 5). The iv BBR dose was 1.0 mg kg⁻¹, and the oral dose was 100 mg kg⁻¹. The concentration of TPGS in the formulation was 2.5%

Fig. 2

Histopathological comparison between test and control rats. Light micrograph samples were taken at 5 h after oral gavage administration of drugs (original magnification, ×100). I Control, oral gavage administration of BBR. II Test, oral gavage administration of BBR formulation containing 2.5% TPGS. The BBR doses were all 100 mg kg⁻¹