Fast and Efficient Screening and Separation Based on AUF-MS Combined With Molecular Docking Technology and Network Pharmacology Method for Potential Xanthine Oxidase Inhibitors From Pinelliae Rhizoma Praeparatum

Abstract

Introduction: Studies show that Pinelliae Rhizoma Praeparatum (PRP) has some pharmacological effects in enhancing immunity and against gout.

Objectives: A mathematical model was created for extraction process optimization, analysis and identification, activity screening, and isolation and purification; moreover, the mechanism of action was studied.

Methods: First, the extraction of PRP was investigated using the gray wolf optimization mathematical regression model; the extraction variables were optimized to maximize the yield. Second, we used network pharmacological analysis to predict potential targets for PRP in treating gout; xanthine oxidase inhibitors (XODIs) were rapidly screened using AUF-MS and enzyme-catalyzed reaction kinetics. The potential antigout effects of the obtained active substances were verified using molecular docking and molecular dynamics simulation analysis. Finally, with activity screening as the guide, an HSCCC method combined with consecutive injection using the UNIFAC mathematical model and semipreparative HSCCC was successfully developed for the separation and purification of XODIs.

Results: The results verified that uridine, guanosine, adenosine, liquiritin, and liquiritigenin of PRP exhibited high biological affinity toward XOD.

Conclusion: This study clarifies the mechanisms of action of a medicinal plant of interest at the molecular level and can provide more opportunities for the discovery and development of new therapeutic drugs from other food resources.

Keywords: Pinelliae Rhizoma Praeparatum (PRP); consecutive HSCCC and UNIFAC mathematical model; molecular docking technique; network pharmacology; xanthine oxidase inhibitors (XODIs).