Search

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.

Nuclear magnetic resonance/liquid chromatography-mass spectroscopy parallel dynamic spectroscopy (NMR/LC-MS PDS) is a method aimed at the simultaneous structural identification of natural products in complex mixtures. In this study, the method is illustrated with respect to 1H NMR and rapid resolution liquid chromatography-mass spectroscopy (RRLC-MS) data, acquired from the crude extract of Anoectochilus roxburghii, which was separated into a series of fractions with the concentration of constituent dynamic variation using reversed-phase preparative chromatography. Through fraction ranges and intensity changing profiles in 1H NMR/RRLC-MS PDS spectrum, 1H NMR and the extracted ion chromatogram (XIC) signals deriving from the same individual constituent, were correlated due to the signal amplitude co-variation resulting from the concentration variation of constituents in a series of incompletely separated fractions. 1H NMR/RRLC-MS PDS was then successfully used to identify three types of natural products, including eight flavonoids, four organic acids and p-hydroxybenzaldehyde, five of which have not previously been reported in Anoectochilus roxburghii. In addition, two groups of co-eluted compounds were successfully identified. The results prove that this approach should be of benefit in the unequivocal structural determination of a variety of classes of compounds from extremely complex mixtures, such as herbs and biological samples, which will lead to improved efficiency in the identification of new potential lead compounds. [ABSTRACT FROM AUTHOR]

The most attractive advantage of dynamic combinatorial chemistry (DCC) is that it can screen the compound library as soon as compounds are synthesized. However, it is very difficult to analyze a dynamic combinatorial library with free probes using the state-of-the art analysis technologies. We report herein a method that uses a resin-immobilizing reversed peptide probe to screen vancomycin derivatives and provides a solution to this problem. [ABSTRACT FROM AUTHOR]

One megastigmane derivative 1, one methyl jasmonate glycoside derivative 2, and two C-28 steroids with 3β,5β-cis-dihydroxyl conformation 3 and 4, together with eight known compounds 5-12 were isolated from the 70% ethanol extract of linseed meal (Linum usitatissimum L). Structures of 1-4 were elucidated by spectroscopic methods including NMR, HRESIMS, and Mo2(OAc)4-induced CD. The absolute configuration of 1 and 3 was determined by observing their induced circular dichroism after addition of Mo2(OAc)4 in DMSO. The absolute configuration of 2 was determined by NOESY experiment together with conformational analysis. The structure of 4a was corrected as 4 by an extensive analysis of its 1D and 2D NMR, in combination with the Mo2(OAc)4-induced CD in DMSO. The effect of all the isolates on nitric oxide (NO) generation by stimulated macrophages was evaluated, and none of them showed active. [ABSTRACT FROM AUTHOR]