Data Mining-Network Pharmacology Reveal TCM Mechanisms In Apical Periodontitis

Traditional Chinese Medicine (TCM) syndrome differentiation and treatment principles provide critical insights for apical periodontitis (AP) management. However, clinical heterogeneity and the polypharmacological complexity of herbal formulations impede standardized therapeutic protocols. This study systematically evaluates the therapeutic efficacy and molecular mechanisms of core TCM herbal pairs in AP treatment. Approved by the Ethics Committee of our Medical University Stomatological Hospital, this study integrated data mining of 53 clinical studies (41 prescriptions, 102 herbs) to identify the core pairing Shengdihuang-Mudanpi (SDH-MDP). Network pharmacology and molecular docking were integrated with in vitro functional assays using inflammatory macrophages (PMA-primed THP-1) and periodontal ligament stem cells (PDLSCs), complemented by in vivo validation in a murine AP model (18–22 g male mice). Notably, SDH-MDP, characterized by "heat-clearing, wind-dispelling, blood-cooling, and pain-relieving" effects, significantly ameliorated AP pathogenesis. Mechanistically, bioactive monomers (paeoniflorin-H, β-sitosterol, benzoylpaeoniflorin) in SDH-MDP exert anti-inflammatory, antioxidant, and apoptosis-inducing effects via bioactive monomers such as paeoniflorin-H, β-sitosterol, and benzoylpaeoniflorin through targeting the AKT1, MMP9, and TNF-α pathways to mediate therapeutic actions against AP. Clinically, SDH-MDP demonstrates excellent in vivo biological safety and exhibits significant anti-inflammatory and promoting bone repair efficacy in both in vitro and in vivo AP models. SDH-MDP emerges as a dual-functional TCM herbal pair for AP, combining potent anti-inflammatory and osteo-regenerative effects with translational relevance, offering a novel therapeutic strategy grounded in TCM theory.