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.
