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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 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).
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pone-0077969-g002: 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).

Mentions: The calculation of BBR and its metabolites distributed in tissues was based on the results of BBR concentration in plasma. The pharmacokinetic profile was represented in Fig.2A and Table 1. According to the data of pharmacokinetics software, the values of t1/2 and Tmax were 14.73±7.28 h and 1.33±0.29 h, respectively. The results of AUC (0-∞) and AUC (0-t) were 86.37±13.57 ng/mL×h, and 75.83±5.60 ng/mL×h, respectively. The value of Cmax was 25.85±7.34 µg/L. In the meantime, abundance of BBR in different tissues was compared with that in plasma within 48h. Profiles were sorted by amounts of BBR in tissues from most to least (Fig.2B–2I).


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 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).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0077969-g002: 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).
Mentions: The calculation of BBR and its metabolites distributed in tissues was based on the results of BBR concentration in plasma. The pharmacokinetic profile was represented in Fig.2A and Table 1. According to the data of pharmacokinetics software, the values of t1/2 and Tmax were 14.73±7.28 h and 1.33±0.29 h, respectively. The results of AUC (0-∞) and AUC (0-t) were 86.37±13.57 ng/mL×h, and 75.83±5.60 ng/mL×h, respectively. The value of Cmax was 25.85±7.34 µg/L. In the meantime, abundance of BBR in different tissues was compared with that in plasma within 48h. Profiles were sorted by amounts of BBR in tissues from most to least (Fig.2B–2I).

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