Exploring the Pharmacological Mechanism of Cinnamomum zeylanicum Fruit Extract in Treating Gingivitis Using Network Pharmacology

Abstract

Background: Cinnamomum zeylanicum (CZ), a traditional Ayurvedic medicinal plant, is known for its anti-inflammatory properties, particularly in the treatment of gingivitis. Despite its recognized efficacy, the precise mechanism of action remains elusive. In this study, we employed a network pharmacology (NP) approach to elucidate the mechanism of action of its bioactive constituents against gingivitis. Objectives: To identify pathways associated with gingivitis that are modulated by bioactive compounds present in CZ fruit using NP Methods: Firstly, target genes of the main bioactive components of CZ were collected from Swiss Target Prediction, Similarity Ensemble Approach Search Server, and Super-PRED. Key genes involved in the pathophysiology of gingivitis were retrieved from Genecards, Online Mendelian Inheritance in Man, and DisGeNET databases. Common targets were identified using Venny 2.1 and used to construct a protein-protein interaction network, visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed with the assistance of bioinformatics tools. Results: The screening process identified 637 target genes of active compounds in CZ fruit extract and 5386 gingivitis-related gene targets. Of these, 286 common targets were identified. In the STRING database, a network consisting of 286 nodes and 5369 edges was constructed. The top 10 genes associated with the activity of CZ included STAT3, TP53, GAPDH, BCL2, IL6, ESR1, HSP90AA1, TNF, MTOR and CASP3. The KEGG pathway analysis revealed 291 significant pathways, suggesting the potential reduction of various inflammatory processes associated with anti-gingivitis activity by CZ fruit extract, with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway identified as the most enriched pathway. Furthermore, the biological processes, cellular components, and molecular functions with the highest enrichment scores were positive regulation of protein kinase B signaling, membrane raft, and protein tyrosine kinase activity, respectively. Conclusions: The results revealed that CZ fruit extract could modulate multiple pathways involved in the pathophysiology of gingivitis suggesting it as a beneficial therapeutic option within traditional medicine for gingivitis by modulating multiple pathways involved in its pathophysiology.