Fermentation-Driven Changes in Phenolic Compounds of Massa Medicata Fermentata

Massa Medicata Fermentata (MMF), a clinically important fermented traditional Chinese medicine for treating gastrointestinal and metabolic disorders, struggles with quality control due to insufficient reliable reference materials. Because phenolic compounds are key ingredients of MMF, this study investigated how fermentation reshapes the phenolic profile of MMF and enhances its bioactivity. Using UPLC-ESI-MS/MS-based metabolomics, we identified 119 phenolic compounds (PCs), 66 of which were previously unreported in MMF. Comparative analysis showed that fermentation significantly remodeled the PCs composition, notably enriching free phenolic acids, methoxylated flavonoids, and flavonoid C-glycosides compared to the unfermented precursor (BMMF). Consistent with these changes, MMF exhibited significantly stronger antioxidant and anti-inflammatory activities than BMMF (p < 0.01). Correlation analysis revealed strong correlations (∣r∣ > 0.8) between specific PCs and enhanced bioactivities. Our work not only clarifies the molecular basis for fermentation-induced efficacy enhancement but also proposes evidence-based phenolic markers to support the quality standardization of MMF.