Deciphering the Pharmacological Potential of Kouqiangjie Formula for the Treatment of Diabetic Periodontitis Based on Network Pharmacology, Machine Learning, Molecular Dynamics, and Animal Experiments.

BACKGROUND

Periodontitis (PD) and type 2 diabetes mellitus (T2DM) represent interlinked global health burdens, commonly causing significant clinical complications when coincident. Therefore, managing both conditions (T2DM with periodontitis, DP) simultaneously poses considerable challenges, necessitating novel therapeutic strategies. KQJF has been clinically proven to treat DP with good efficacy, but its pharmacological substances and targets are not clear and urgently need to be clarified.

AIM

To define the potential active components and targets of KQJF for the treatment of DP.

MATERIALS AND METHODS

The investigation commenced with the application of UPLC-Q-TOF/MS analysis to delineate the active constituents of KQJF and their associated targets in addressing DP. Additionally, the research incorporated subsequent methodologies such as machine learning, network pharmacology, molecular docking, molecular dynamics simulations, and a DP rat model was established and validated by in vivo experiments using H&E staining, immunohistochemistry, quantitative real-time PCR, and Western blot.

RESULTS

KQJF was found to contain 49 prototype compounds and 121 metabolites with potential activity against PD and T2DM. Network pharmacology revealed 66 overlapping genes between the pharmacological targets of KQJF and known targets of PD and T2DM. Further exploration through PPI network and enrichment analyses illuminated the involvement of multi-target and multi-pathway mechanisms. Molecular docking and dynamics simulations confirmed the robust interactions between key compounds within KQJF and proteins associated with the diseases. In vivo validation demonstrated that KQJF treatment ameliorated DP-associated histopathological changes and modulated the expression of crucial proteins (including ABCG2, CCND1, CDKN1B, HIF1A, and PIK3R1) in a DP rat model.

CONCLUSION

In summary, KQJF exhibits potential therapeutic benefits for DP through a multi-component and multi-target approach, potentially offering a novel integrative treatment strategy. This study underscores the importance of integrating traditional medicine with modern molecular techniques to explore novel therapeutic avenues for complex comorbid conditions, providing a blueprint for future pharmacological explorations.