Deciphering the Pharmacological Potential of Kouqiangjie Formula for the Treatment of Diabetic Periodontitis Based on Network Pharmacology, Machine Learning, Molecular Dynamics, and Animal Experiments.
Yeke Wu, Jiawei Li, Min Liu, Ranran Gao, Huijing Li, Yunfei Xie, Qiongying Hu, Jing Wei, Lixing Zhao, Li Li
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引用次数: 0
Abstract
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.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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