Tissue Distribution of Berberine and Its Metabolites after Oral Administration in Rats

作者：Xiang‐Shan Tan, Jingyi Ma, Ru Feng, Chao Ma, Wenjing Chen, Yupeng Sun, Jie Fu, Min Huang, Chi‐Yu He, Jia‐Wen Shou, Wen‐Yi He, Yan Wang, Jian‐Dong Jiang · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0077969 · 被引用次数：258 · 研究领域：Berberine and alkaloids research、Alkaloids: synthesis and pharmacology、Plant-based Medicinal Research

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 ...