Study on drug-target binding kinetics profiles of flavonoids in Chrysanthemum morifolium and xanthine oxidase / 中国中药杂志

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.

[Study on binding kinetics profiles of tea polyphenols-α-glucosidase interaction].

The combination index(CI) method was used to evaluate the combination inhibition mechanism of epicatechin gallate(ECG) and other tea polyphenols [epigallocatechin gallate(EGCG) and gallocatechin gallate(GCG)] on α-glucosidase. Herein, using ECG as research object, the surface plasmon resonance(SPR) analysis were employed to study the binding affinities and kinetic parameters of three tea polyphenols components on α-glucosidase, respectively. The concentration-time curve mathematical model of the drug in the unstirred water layer(the adjacent region of α-glucosidase) established previously by our group was used to evaluate the concentration-time curves of the tea polyphenols in the α-glucosidase vicinity. The prediction model of drug-α-glucosidase binding kinetics established by our group was used to evaluate the dynamic process of drug-α-glucosidase binding kinetics of different oral administration processes of ECG. Using acarbose as a reference, the accuracy of the model prediction was judged based on the difference between the prediction results and the actual clinical performance. Using the mathematical model of drug-α-glucosidase interaction, the drug-α-glucosidase binding kinetic characteristic curves of ECG in different administration processes were obtained, which indirectly proved that the synergistic effect of multi-component combination of traditional Chinese medicine and the clinical characteristics of repeat administration were scientific and reasonable.

Thinking on TCM literature evaluation methods and techniques based on mass information / 中国中西医结合杂志

The necessity and feasibility of TCM literature evaluation based on mass information of TCM literature was discussed in this paper. Beginning with the description on current situation of mass TCM literature information research, the authors offered a tentative plan for evaluating scientific and technologic TCM literature, its method and technique, and systematically analyzed the key issues, such as the subjects selection, documents screening and sorting, literature analysis, and development of software analysis platform, then, the methodology and the technology for constituting the mass TCM literature information based evaluation system was systemically clarified.