Berberine Bbr

1 Introduction
Berberine (BBR), an isoquinoline alkaloid (Fig. 1), is isolated from many medicinal herbs, such as Coptidis rhizome (Coptis chinensis Franch.) and Cortex phellodendri (Phellodendron chinense C.K.Schneid.) [1]. BBR has been used as a medicine for a long time, it is used to treat microbial infection, diarrhea, and gastrointestinal (GI) diseases due to its antibacterial, antidiarrheal and strong antidotal properties [2, 3]. In recent years, much focus has been put on its other new bioactivities, such as antihyperlipidaemic [4, 5], antidiabetic [6], and anticancer properties in several cancer lines including breast [7], thyroid [8], bladder [9] and hepatoma [10]. Despite the promising bioactivities, BBR has poor oral bioavailability, which seriously limits its medical application. Therefore, in order to expand the clinical uses of BBR by developing suitable formulations, the fundamental work was to investigate the factors

Materials and methods
2.1. Materials
Cell culture reagents and buffers were purchased from Life Technologies, Inc. (Carlsbad, CA). Berberine (purity 99%) were purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Other chemicals were purchased from Sigma Chemical Company (St. Louis, MO), Aladdin Reagents Co., Ltd (Shanghai, China) and Guoyao Chemical Co., Ltd. (Shanghai, China). HPLC grade water was purchased from Watsons (Guangzhou, China). All other chemicals were of HPLC or analytical grade.
2.2. Transport study in Caco-2 cell model
2.2.1. Cell culture
Caco-2 cell was provided (passage 32–36) by School of Pharmaceutical Science at Sun Yet-Sen University. Cells were grown in an atmosphere of 5% CO2 and 90% relative humidity at 37°C. They were routinely maintained in Dulbecco’s modified Eagle’s medium (DMEM) containing 4.5 g/l D-glucose, 10% fetal bovine serum, 1% nonessential amino acids, 1% L-glutamine, 1 mM Sodium pyruvate, 100 U/ml penicillin, and 100 g/ml