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

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.