Screening of Bioactive Ingredients in Ligusticum Chuanxiong Hort for Protection against Myocardial Ischemia.

BACKGROUND/AIMS: To study the spectrum-effect relationship and effective components of Ligusticum Chuanxiong Hort. (LCH) on the protection of canine myocardial ischemia. METHODS: Fingerprint spectrum of LCH extracts was developed using high performance liquid chromatography (HPLC), and a canine model of acute myocardial ischemia was established by ligating the coronary artery. Bivariate correlation analysis and multivariate regression analysis were used to correlate the pharmacodynamics of LCH extract and its common peaks in HPLC. RESULTS: The bioactive components of LCH were ligustrazine, ferulic acid, cnidilide and ligustilide. Ligustrazine and ferulic acid could significantly reduce serum lactic acid in canine model of acute myocardial ischemia, while ligustilide could significantly reduce the elevation of serum free fatty acid. CONCLUSIONS: The spectrum-effect relationship study shows that the effective components of LCH are ligustrazine, ferulic acid, cnidilide and ligustilide, which have protective effect on myocardial ischemia.

Chronopharmacokinetics of Erlotinib and Circadian Rhythms of Related Metabolic Enzymes in Lewis Tumor-Bearing Mice.

OBJECTIVE: The purpose of the current study was to investigate the effect of the dosing time on the pharmacokinetics of erlotinib and the circadian rhythms of the metabolism enzymes in tumor-bearing mice. METHODS: Female C57BL mice were randomly assigned to six groups. Erlotinib was orally administrated to the mice in each group at six different times of day. The plasma concentration of erlotinib was determined through a high-performance liquid-chromatographic assay, and the total mRNA was extracted from liver tissues to determine the expression of the mRNA of the related drug metabolism enzymes by qRT-PCR. RESULTS: The results indicated that AUC0-24 h and MRT0-24 h were the lowest in the 20:00 group (P < 0.01). T max of the 13 HALO (hour after light onset), 17 HALO and 21 HALO groups was higher than that of the 1 HALO and 5 HALO groups (P < 0.01). CL of the light-phase groups was lower than that of the dark-phase groups (P < 0.01). The peak value of C max appeared in the 5 HALO group (P < 0.01). The mRNA levels of Cyp3a11, Cyp3a13 and Cyp1a2 were generally higher during the afternoon and the dark phase. CONCLUSION: Circadian rhythm plays a critical role in the pharmacokinetics of erlotinib in mice, and the mechanisms may be attributed to gene expression rhythms of drug-metabolizing enzymes in liver tissues.

Liquid chromatography tandem mass spectrometry in study of the pharmacokinetics of six steroidal saponins in rats.

A rapid, simple and sensitive high-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous determination of six main steroidal saponins in Paris polyphylla in rat plasma. Ginsenoside Rg3 was selected as the internal standard (IS). Plasma samples were pretreated with protein precipitation, and the separation was achieved on a reverse phase Agilent poroshell120 EC-C18 column using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid. The triple quadruple mass spectrometer was set in negative electrospray ionization mode and multiple reaction monitoring (MRM) was used for six steroidal saponins quantification. The precursors to produce ion transitions monitored for polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII, dioscin, gracillin and IS were m/z 899.5>853.4, 1059.5>1013.5, 783.4>737.4, 1075.5>1029.5, 913.5>867.4, 929.5>883.4 and 819.5>783.4, respectively. The intra- and inter-day precisions (RSD%) were less than 13% and the average extraction recoveries ranged from 85% to 97.0% for each analyte. Six steroidal saponins were proved to be stable during sample storage, preparation and analytical procedures. The established method was employed for simultaneous quantification and successfully used for the first time for the pharmacokinetics evaluation of the six main compounds after intragastric administration of P. polyphylla extract in Sprague-Dawley rats.

A study on the chiral recognition mechanism of enantioseparation of adrenaline and its analogues using capillary electrophoresis.

The purpose of this paper was to study the chiral recognition mechanism of enantioseparation of adrenaline and its analogues using capillary electrophoresis. The enantiomeric separation of adrenaline and its analogues has been developed using beta-cyclodextrins as the chiral selectors. All the tested compounds were separated under the same experimental conditions to study the chiral recognition mechanisms, using a low-pH buffer (50 mM Tris buffer at pH 2.5). By means of molecular docking the inclusion course between beta-cyclodextrins and enantiomers was investigated and thus the interaction energy was obtained by molecular mechanics calculations. The results suggest that the difference in interaction energy for the side chain part is most likely responsible for enantiomeric separation.