Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design / 中国中药杂志

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

A new spectrophotometric method for the determination of fluvoxamine maleate in pure form and in pharmaceutical formulation.

A simple, accurate and highly sensitive spectrophotometric methods are proposed for the rapid and accurate determination of fluvoxamine maleate (FXA) using bromocressol green (BCG), methyl orange (MO) and bromothymol blue (BTB). The developed methods involve formation of stable yellow colored chloroform extractable ion-associate complexes of the amino derivative (basic nitrogen) of the FXA with three sulphonphthalein acid dyes, namely; BCG, MO and BTB, in potassium hydrogen phthalate buffer pH 3.3, 3.6 and 3.4 respectively. The ion-associates exhibit absorption maxima at 420, 420 and 410 nm for BCG, MO and BTB, respectively. FXA can be determined up to 2.0–16, 2.0–15 and 2.0–20 μgmL−1 for BCG, MO and BTB, respectively. The effect of optimum conditions via pH on the ion pair formation, reagent concentration, time and temperature, and solvent was studied. The composition of the ion pairs was found 1:1 by Job’s method. The low relative standard deviation values indicate good precision and high recovery values. These methods have been successfully applied for the assay of FXA in pure form and in pharmaceutical formulations and the results are in good agreement with those obtained by the official method.