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

Tan XS, Ma JY, Feng R, Ma C, Chen WJ, Sun YP, Fu J, Huang M, He CY, Shou JW, He WY, Wang Y, Jiang JD - PLoS ONE (2013)

Bottom Line: However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients.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.

View Article: PubMed Central - PubMed

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.

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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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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pone-0077969-g003: 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).

Mentions: After oral administration, metabolites of BBR were found in the liver, kidneys, lungs, muscle, heart and pancreas. Most of the metabolites reached the tissue within 4 h after dosing. Liver was the highest carrier, followed by kidneys, lungs, muscle, heart and pancreas. All of the metabolites were Phase I metabolites, and M1 and M2 were predominated. Accordingly, abundance of metabolites in tissues was compared with that of BBR in the tissue (Fig.3A to 3F, and Table 3), in order to learn the tissue distribution of BBR.


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

Tan XS, Ma JY, Feng R, Ma C, Chen WJ, Sun YP, Fu J, Huang M, He CY, Shou JW, He WY, Wang Y, Jiang JD - PLoS ONE (2013)

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).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815028&req=5

pone-0077969-g003: 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).
Mentions: After oral administration, metabolites of BBR were found in the liver, kidneys, lungs, muscle, heart and pancreas. Most of the metabolites reached the tissue within 4 h after dosing. Liver was the highest carrier, followed by kidneys, lungs, muscle, heart and pancreas. All of the metabolites were Phase I metabolites, and M1 and M2 were predominated. Accordingly, abundance of metabolites in tissues was compared with that of BBR in the tissue (Fig.3A to 3F, and Table 3), in order to learn the tissue distribution of BBR.

Bottom Line: However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus