Computational and preliminary screening of anti-caries active compounds of Caesalpinia sappan

Dental caries is a significant global oral health problem, primarily caused by Streptococcus mutans (S. mutans). Although previous studies have indicated that Caesalpinia sappan (CS) exhibits anti-caries properties, its specific anti-caries active compounds remain largely unidentified. This study aimed to identify the potential anti-caries components of CS through an integrated strategy involving bioassay-guided isolation targeting S. mutans, UPLC-MS/MS, network pharmacology, molecular docking, and molecular dynamics simulation. Bioassay-guided isolation led to the identification of 33 compounds in fraction 5 from CS, among which brazilin showed the highest content and effectively inhibited biofilm formation and acid production by S. mutans. Network pharmacology analysis predicted 11 active ingredients in CS, including brazilin, targeting 7 potential targets related to dental caries: AKT1, EGFR, BCL2, PTGS2, MMP9, ERBB2, and HSP90AA1, as well as two pathways—nitrogen metabolism and calcium signaling. Molecular docking revealed strong binding affinities of brazilin to PTGS2, EGFR, MMP9, GtfC, GtfD, and GbpC. Further, molecular dynamics simulation revealed strong stability between brazilin and PTGS2, GtfC. Together, these findings not only clarify the anti-caries chemical constituents of CS and their potential mechanisms of action, but also provide new insights into the bioactive components and mechanisms of natural plant-derived medicines for the prevention and treatment of dental caries.