Preliminary screening of anti-caries active compounds of Caesalpinia sappan

Dental caries represents a major global oral health issue, primarily caused by Streptococcus mutans ( S. mutans ). While previous studies have indicated that Caesalpinia sappan ( CS ) possesses anti-caries activity, its specific anti-caries chemical constituents remain largely unexplored. This study aimed to identify the potential anti-caries constituents of CS using an integrated approach combining network pharmacology, ultra-Performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), bioassay-guided isolation targeting S. mutans , and molecular docking. We identified a total of 35 active ingredients in CS , sharing 79 potential therapeutic targets associated with dental caries, including AKT1, EGFR, BCL2, PTGS2, MMP9, ERBB2, and HSP90AA1. Key pathways implicated included nitrogen metabolism and calcium signaling. Bioassay-guided isolation yielded 33 compounds in the fifth fraction from CS . However, only brazilin overlapped with the network pharmacology-predicted key ingredients. Brazilin effectively inhibited biofilm formation and acid production by S. mutans and demonstrated strong binding affinity to EGFR, BCL2, and MMP9 in molecular docking analysis, with docking scores all below -7 kcal/mol. Collectively, these findings not only elucidate the anti-caries chemical constituents of CS and their potential mechanisms of action but also provide novel insights into the bioactive constituents and mechanisms underlying natural plant-derived medicines for the prevention and treatment of dental caries.