Discovery of Q‐Markers of Mudan Granules by Chemical Profile, Pharmacokinetics, Neuroprotective Effect Evaluation, and Network Pharmacology

ABSTRACT Mudan granules (MDs) are a widely used Chinese patent medicine for treating diabetic peripheral neuropathy (DPN). TCM quality is the basis to ensure its efficacy; however, the current quality standard for MD relies on the control of only two constituents derived from the minister drugs. Therefore, it is necessary to establish a more comprehensive quality evaluation system based on rational quality markers (Q‐markers). In this study, Q‐markers of MD were discovered through systematic evaluations. Thirty‐seven compounds were newly characterized in MD by UPLC‐QTOF‐MS. Among all the 173 constituents in MD, 64 were found to be absorbed into the bloodstream and/or sciatic nerve of rats in prototype. The contents of 24 candidate Q‐markers were determined, and the pharmacokinetics features of nine ones were analyzed by two developed UPLC‐MS methods. Six candidate Q‐markers were first found to exhibit protective effects on Schwann cells against the injury of high glucose/lipid. Finally, nine Q‐markers were screened, and network pharmacology analysis showed that the enriched pathways for these nine Q‐markers covered the major DPN‐related pathways for the full set of 173 constituents. The results provide important evidence for improving the quality control system of MD and reference for discovering Q‐markers of other TCM prescriptions.