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/MSn-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.

Current knowledge and pharmacological profile of berberine: An update

“…Moreover, the concentration of berberine as well as its bioactive metabolites was found to be higher in organs as compared to its concentration in the blood after oral administration. The organ distribution of berberine is rapid with maximum distribution in liver, followed by kidneys, muscle, lungs, brain, heart, pancreas and with least distribution in fat where it remains relatively stable for 48h (Tan et al, 2013).…”

Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS

“…Several liquid chromatography coupled ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) and liquid chromatography/electrospray ionization/ion trap mass spectrometry methods have developed for tissue distribution or pharmacokinetics study of berberine and its metabolites after oral administration [10,11]. However, currently, no UPLC-MS/MS method for the determination of berberrubine in plasma and tissue has been reported.…”

Effect of food on the Oral Bioavailability of Berberine and Monacolin Administered in Combination in Healthy Male Volunteers

“…However, the presence of multiple peaks in the plasma concentration-time profile, indicating an enterohepatic circulation for berberine, as observed in other previous investigations [24,25], prevented the calculation of K e (elimination rate constant) , and thereby of AUC inf and t 1/2, (half-life). Significant differences between fed and fasted conditions were observed in the plasma concentration-time profile of berberine.…”