Tissue distribution of berberine and its metabolites after oral administration in rats - PubMed (original) (raw)

. 2013 Oct 31;8(10):e77969.

doi: 10.1371/journal.pone.0077969. eCollection 2013.

Jing-Yi Ma, Ru Feng, Chao Ma, Wen-Jing Chen, Yu-Peng Sun, Jie Fu, Min Huang, Chi-Yu He, Jia-Wen Shou, Wen-Yi He, Yan Wang, Jian-Dong Jiang

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Tissue distribution of berberine and its metabolites after oral administration in rats

Xiang-Shan Tan et al. PLoS One. 2013.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. BBR mass spectrographic behavior and its metabolism in tissues.

1A Structure of BBR 1B Mass spectrographic behavior of BBR 1C Representative EIC chromatogram of BBR and its metabolites in liver (8 h) in rat.

Figure 2

Figure 2. Tissue distribution of BBR.

2A Plasma concentration-time profile of BBR after oral administration of 200 mg/kg in 48 h (n = 6) 2B Profiles of BBR in liver distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2C Profiles of BBR in kidney distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2D Profiles of BBR in muscle distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2E Profiles of BBR in lung distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2F Profiles of BBR in brain distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2G Profiles of BBR in heart distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2H Profiles of BBR in pancreas distribution in SD rats after oral administration of 200 mg/kg (n = 6) 2I Profiles of BBR in fat distribution in SD rats after oral administration of 200 mg/kg (n = 6).

Figure 3

Figure 3. Tissue distribution of metabolites of BBR.

3A Profiles of BBR and its metabolites in liver distribution in SD rats after oral administration of 200/kg (n = 6) 3B Profiles of BBR and its metabolites in kidney distribution in SD rats after oral administration of 200 mg/kg (n = 6) 3C Profiles of BBR and its metabolites in lung distribution in SD rats after oral administration of 200 (n = 6) 3D Profiles of BBR and its metabolites in muscle distribution in SD rats after oral administration of 200 mg/kg (n = 6) 3E Profiles of BBR and its metabolites in pancreas distribution in SD rats after oral administration of 200 mg/kg (n = 6) 3F Profiles of BBR and its metabolites in heart distribution in SD rats after oral administration of 200 mg/kg (n = 6).

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The project was supported by National Science and Technology Special Projects (2012ZX09301-002-001, 2012ZX09301-002006), and the financial support from the National Natural Science Foundation of China (No. 30873115and 81072611). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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