Multi-Compartment Electrophoresis Separation Technology Screening Synergistic α-Glucosidase Inhibitors From Schizandra Chinensis

Synergistic drug combination can perturb biological networks synergistically to treat a variety of disease and is considered to be advanced treatment strategies.Identification of synergistic therapies mechanism is critical to treat various diseases.Research strategy of synergistic effect is now focused on biology experiments,which observed pharmacological phenomena with limited components.While so far,it remains a challenge to accurately determine synergistic component combination due to their complexity and lack of effective screening method with the merit of rapidity,simplicity and reproducibility.Here we developed a multi-compartment electrophoresis separation system(MCESS)coupled with HPLC-MS/MS method for rapid screening possible synergistic components.The system is consisted of multi-compartment separated by membranes and target-synergistic ligand complexes in complicated matrix were rapidly separated from sample compartment to receptor compartment by electrophoresis under the physiological conditions and low voltage.The synergistic candidates were identified and quantified with HPLC-MS/MS after dissociation of the complexes.The initial three-dimensional structure of protein was remained in the experimental procedures,it is beneficial for maintain intrinsic activity of enzyme.The developed approach was validated by screening known components Indometacin and Dflunisal binding to human serum albumin.We tried to screen kinds of known target protein inhibitors,of which acarbose was screened with 70-80%of mobility and 0.3-6.6%of reproducibility.Finally,the established approach was applied for screening the synergistic effect inhibitors of α-glucosidase from Schizandra Chinensis.Nine components were screened as potential synergistic components on the inhibition of α-glucosidase from the Schizandra Chinensis extract and will be identified as potential α-glucosidase inhibitors that associated with diabetes.Overall,this study both identifies a new specific combination treatments for disease and the proposed approach is an effective way to screen synergistic component combination.The proposed approach is great significant for dissecting synergistic mechanism of clinical medicine.