Molecular dynamics simulation studies of transmembrane transport of chemical components in Chinese herbs and the function of platycodin D in a biological membrane

Objective:To study the transmembrane transport of chemical components of Chinese herbs and to explore the function of platycodin D (PD) on biomembranes.Methods:Interaction between PD and the dipalmitoylphosphatidylcholine (DPPC) bilayer was reproduced by molecular dynamics simulation with the Martini force field.A model validation and methodological study were first performed,and were based on simulation investigations of transmembrane transport for three herbal compounds with distinct hydrophilic properties.Results:PD increased the mobility of the DPPC bilayer since its aglycone strongly interacted with the hydrophobic layer,which broke the structure of the gate layer,and weakened the ordered performance of hydrophobic tails.Conclusion:The Martini force field was successfully applied to the study of the interaction between herbal compounds and a biological membrane.By combining the dynamics equilibrium morphology,the distribution of drugs inside and outside the biomembrane,and the interaction sites of drugs on the DPPC bilayer,factors influencing transmembrane transport of drugs were elucidated and the function of platycodin D in a biological membrane was reproduced.

An HPLC-MS/MS method for the quantitative determination of platy-codin D in rat plasma and its application to the pharmacokinetics of Platycodi Radix extract

AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD. METHOD: Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge. Madecassoside was used as the internal standard(IS). Chromatographic separation was achieved on an ODS column(100 mm × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of acetonitrile/water(30 : 70, V/V) containing 0.1 mmol L 1ammonium acetate at a flow rate of 0.25 mL min 1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min. The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6→469.2 for PD and of m/z 973.6→469.2 for madecassoside(IS), respectively. RESULTS: The calibration curve was linear from 5 to 2 000 ng mL 1(r2>0.99) with a lower limit of quantification(LLOQ) of 5 ng mL 1. The intra- and inter-day precision(relative standard deviation, RSD) values were below 15% and the accuracy(relative error, RE) was from 15% to +15% at three quality control(QC) levels. Plasma concentrations of PD were determined for 24 h after i.v. administration of PD, and oral administration of PD and PRE, respectively. The absolute oral bioavailability of PD in rats was found to be(0.48 ± 0.19)% when administered PD, and to be(1.81 ± 0.89)% when administered PRE. CONCLUSION: The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.

Dissipative Particle Dynamics Study on Platycodin's Solubilization Enhancing Effect Towards Five Drug Components

In this study,a dissipative particle dynamics mehtod was used to study the solubilization enhancing effect of platycodin towards 5 different drug components.Two factors were mainly considered,including the ,XlogP value of drug components and the sugar chain length of platycodin.As a result,it was found that there was an optimal drug XlogP value for the solubilization enhancing effect of platycodin,and it was different between the drug's own XlogP value and the optimal drug XlogP value of platycodin that determines the solubilization enhancing effect.