Characterization of binding interaction between magnesium isoglycyrrhizinate and human serum albumin.

Magnesium isoglycyrrhizinate (MgIG) is the magnesium salt of 18ß-glycyrrhizic acid extracted from licorice, a Chinese traditional medicine. The pharmacokinetic characteristics of MgIG have been widely studied; nevertheless, its target protein and mechanism of action remain unclear. Therefore, the objective of present work was to determine the characteristics of binding between human serum albumin (HSA) and MgIG. The formation of HSA-MgIG complex was studied using spectrometric techniques, LC-MS/MS, and molecular docking calculations. The results of fluorescence study demonstrated the quenching mechanism is definitely static. The negative thermodynamic parameters suggested that the interaction is enthalpically driven and occurs spontaneously. Binding density and probe displacement analysis suggested that MgIG bound to HSA at a single site, determined to be site I. The mean albumin binding rate of MgIG with HSA concentration ranged from 35 to 50 g·L-1 reached 85.6%. Molecular docking analysis revealed the major residues and interaction forces involved in formation of HSA-MgIG complex, corresponding with the experimental results.

Metabonomics study on Polygonum multiflorum induced liver toxicity in rats by GC-MS.

Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L-threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D-glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What's more, liver injury of alcohol extraction group was more serious than group of water extraction.

Metabolomics analysis in rats after administration of Datura stramonium.

This study aimed to evaluate the effect of Datura stramonium on rats by examining the differences in urine and serum metabolites between Datura stramonium groups and control group. SIMCA-P+12.0.1.0 software was used for partial least-squares discriminant analysis (PLS-DA) to screen for the differential metabolites. Fifteen metabolites in urine including malonic acid, pentanedioic acid, D-xylose, D-ribose, xylulose, azelaic acid, threitol, glycine, butanoic acid, D-mannose, D-gluconic acid, galactonic acid, myo-inositol, octadecanoic acid, pseudouridine and ten metabolites in serum including alanine, butanedioic acid, L-methionine, propanedioic acid, hexadecanoic acid, D-fructose, tetradecanoic acid, D-glucose, D-galactose, oleic acid were selected as the characteristic metabolites. The PLS-DA scores plot indicated that serum and urine metabolites have a variety of changes among low dose group, high dose group and control group. These metabolites were related with amino metabolism, lipid metabolism and energy metabolism. The result reflected the relationship between metabolites in rat fluid and Datura stramonium spectra. Potential differences in metabolites and metabolic pathway analysis showed that the establishment of urine and serum metabolomics methods for further evaluating drug has great significance.

Effect of kanglaite on rat cytochrome P450.

CONTEXT: Kanglaite (KLT) is an oily substance extracted from Coix lacryma-jobi Linn. (Cramineae) and has been proved to significantly improve the life span and quality of life of patients, when combined with chemotherapy, radiotherapy, or surgery. OBJECTIVE: The purpose of this study was to find out whether KLT influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4) by using cocktail probe drugs in vivo. MATERIALS AND METHODS: A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), bupropion (20 mg/kg), tolbutamide (5 mg/kg), omeprazole (20 mg/kg), and midazolam (10 mg/kg), was given as oral administration to rats treated with 7 d intraperitoneal injection of KLT. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0 (SPPS Inc., Chicago, IL). RESULTS: In the experiment, there was a statistically significant difference in the t1/2, Cmax, AUC(0-∞), and CL for phenacetin, bupropion, tolbutamide, omeprazole, and midazolam. Our study showed that treatment with multiple doses of KLT had induction effect on rat CYP1A2, while CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activities had been inhibited after multiple doses of KLT treatment. CONCLUSIONS: KLT can either induce or inhibit activities of CYP. Therefore, caution is needed when KLT is co-administration with some CYP substrates in clinic, which may result in herb-drug interactions.

Development of LC-MS determination method and back-propagation ANN pharmacokinetic model of corynoxeine in rat.

Corynoxeine(CX), isolated from the extract of Uncaria rhynchophylla, is a useful and prospective compound in the prevention and treatment for vascular diseases. A simple and selective liquid chromatography mass spectrometry (LC-MS) method was developed to determine the concentration of CX in rat plasma. The chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 µm) column with acetonitrile-0.1% formic acid in water as mobile phase. Selective ion monitoring (SIM) mode was used for quantification using target ions m/z 383 for CX and m/z 237 for the carbamazepine (IS). After the LC-MS method was validated, it was applied to a back-propagation artificial neural network (BP-ANN) pharmacokinetic model study of CX in rats. The results showed that after intravenous administration of CX, it was mainly distributed in blood and eliminated quickly, t1/2 was less than 1h. The predicted concentrations generated by BP-ANN model had a high correlation coefficient (R>0.99) with experimental values. The developed BP-ANN pharmacokinetic model can be used to predict the concentration of CX in rats.