title: Tissue distribution of berberine and its metabolites after oral administration in rats.
abstract: Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiang-Shan
authors.initials: XS
authors.lastname: Tan
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Ma
authors.forename: Ru
authors.initials: R
authors.lastname: Feng
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Chen
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: He
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Shou
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001599:Berberine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: C055785:jatrorrhizine; D001599:Berberine; C115958:berberrubine; C477156:thalifendine