Characterization of oil/water partition coefficient of chishao terpene glucoside components based on contribution rate of representative components for myocardial ischemia / 中国中药杂志

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.

Discovery and verification of representative ingredients of Chishao terpene glucoside components against ischemia and hypoxia injury / 药学学报

The discovery and verification of components are prerequisites for developing of component preparations. The molecular docking technique and pharmacodynamic activity evaluation provide effective methods for the discovery and verification of the representative components of Chishao terpene glucoside components (CSTGCS) against ischemia and hypoxia injury. The chemical constituents of CSTGCS were analyzed qualitatively by UPLC-TOF/MS/MS. Main chemical constituents were docked with key receptor proteins of myocardial ischemia to preliminarily screen anti-ischemia active ingredients, and screening for main active ingredients with Libdockscore. Then a H9c2 cell hypoxia injury model was established, and creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) were determined to screen the representative combinations in CSTGCS. In addition, apoptosis index, apoptotic protein expression and mitochondria-associated mRNA levels were determined to verify the inhibition of the representative components (RCS) on the apoptosis of hypoxic cells. Eventually, the representative components of CSTGCS were determined. The results showed that paeoniflorin, albiflorin, benzoyl paeoniflorin and oxypaeoniflorin were considered to be the main active components because of their high matching with target proteins (4TWT, 3O4O, 4KZN, 1M9J) in space and energy. There was no statistical difference in regulating CK, LDH, SOD, MDA levels and maintaining mitochondrial function as well as inhibiting cell apoptosis between CSTGCS group and RCS group (paeoniflorin + albiflorin + benzoyl paeoniflorin combination). Therefore, paeoniflorin, albiflorin and benzoyl paeoniflorin were selected as the most representative ingredients of CSTGCS against ischemia and hypoxia injury, providing a basis for the overall properties of the components and formulation of CSTGCS.