Mechanism of the treatment of periodontitis by Lycii Cortex based on network pharmacology and experimental validation
10.3760/cma.j.cn121382-20240322-00410
- VernacularTitle:基于网络药理学及实验验证探讨地骨皮治疗牙周炎的作用机制
- Author:
Xin ZHANG
1
;
Baoyu LI
Author Information
1. 天津医科大学第二医院口腔科，天津 300211
- Keywords:
Periodontitis;
Lycii Cortex;
Network pharmacology;
Mechanism of action
- From:
International Journal of Biomedical Engineering
2024;47(4):375-381
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of action of Lycii Cortex in the treatment of periodontitis based on network pharmacology and experimental validation. Methods:Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was used to screen the drug components of Lycii Cortex. Swiss Target Prediction was used to predict the action targets of the drug components. GeneCards was used to obtain the disease targets of periodontitis. Venny 2.1 was used to obtain the intersecting targets. Protein-protein interaction (PPI) network analysis was performed using the STRING, and network diagrams were constructed using Cytoscape. Gene ontology (GO) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed using Metascape. The Cytoscape software was used to construct "drug-target-pathway" network diagrams. The rats were randomly divided into model group and treatment group, with 5 rats in each group. After modeling for 8 weeks, the treatment group was injected with 1 ml of Lycii Cortex (150 mg Lycii Cortex Granules were dissolved in 1 ml water), and the model group was injected with the same amount of normal saline locally for 4 weeks. Results:A total of 10 active components of Lycii Cortex were founded. These components acted directly on 55 disease targets through multiple pathways to treat periodontitis. The results showed that β-sitosterol, stigmasterol, scopoletin, chrysin, atropine, and ivytin were the core components, and V-Rel reticuloendotheliosis hyperplasia viral oncogene homolog A (RELA), B-cell lymphoma-2 (Bcl-2), prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, cysteinyl aspartate specific proteinase-3 (CASP3), tumor protein 53 (TP53), and nuclear receptor coactivator 2 (NCOA2) were important targets. GO analysis revealed that the most likely biological process (BP) associated with the intersecting genes was mainly involved in the response to steroid hormones, cellular response to organic ring compounds, programmed cell death positive regulation, response to hormones, apoptosis signaling pathway, leukocyte apoptotic process, positive regulation of neuronal apoptotic process, response to oxygen levels, positive regulation of apoptotic process, etc. The cellular component (CC) of the Lycii Cortex was mainly involved in the outer membrane of organelles, outer membrane, transcriptional regulatory complex, outer membrane of mitochondria, RNA polymerase Ⅱ transcriptional regulatory complex, mitochondrial membrane, membrane rafts, membrane microregion, perinuclear region of cytoplasm, etc. The molecular function (MF) of the Lycii Cortex was mainly involved in protein structural domain-specific binding, transcription factor binding, cysteine-type endopeptidase activity involved in apoptotic signaling pathway, DNA-binding transcription factor binding, RNA polymerase Ⅱ-specific DNA-binding transcription factor binding, cysteine-type endopeptidase activity involved in apoptotic process, general transcription initiation factor binding, ubiquitin protein ligase binding, ubiquitin-like protein ligase, etc. The results of KEGG analysis suggested that dermatophytes were mainly involved in the apoptotic process through p53, apoptosis, advanced genetically engineered end products and their receptors (AGE-RAGE), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), interleukin-17 (IL-17), hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling pathways for the treatment of periodontitis. Animal experiments showed that diclofenac could significantly improve periodontitis, as well as improve the expression levels of RELA, Bcl-2, PTGS2, JUN, CASP3, TP53, and NCOA2. Conclusions:Lycii Cortex mainly regulates enzymatic activity, anti-inflammatory, and other biological processes such as RELA, BCL2, PTGS2, JUN, CASP3, TP53, NCOA2, and other disease targets of the signaling pathways such as p53, apoptosis, AGE-RAGE, PI3K-Akt, IL-17, HIF-1, TNF, MAPK, and NF-κB, etc., to treat periodontitis.
