European Journal of Biomedical and Pharmaceutical Sciences

INTEGRATED miRNA–TARGET NETWORK ANALYSIS REVEALS ANTI-ATHEROSCLEROTIC MECHANISMS OF SIKKANCHAR MANAPAGU: AN IN SILICO SYSTEMS PHARMACOLOGY STUDY

Seethaladevi A.*, Varunapriya M., Balamurugan A.

ABSTRACT

Background: Atherosclerosis is a chronic inflammatory vascular disorder characterized by endothelial dysfunction, lipid accumulation, oxidative stress, and immune dysregulation. Traditional Siddha formulations containing medicinal herbs with anti-inflammatory and antioxidant properties may offer multi-target therapeutic benefits in cardiovascular disorders. Sikkanchar Manapagu, prepared using Zingiber officinale, Mentha arvensis, and Citrus limon, contains bioactive phytochemicals with potential cardioprotective activity. Objective: To investigate the miRNA-mediated molecular mechanisms underlying the anti-atherosclerotic potential of Sikkanchar Manapagu using integrated network pharmacology and bioinformatics analysis. Methods: Major phytoconstituents of Sikkanchar Manapagu were identified from published literature and phytochemical databases. Compound-associated targets were predicted using SwissTargetPrediction. Atherosclerosis-associated genes were retrieved from GeneCards and DisGeNET. Overlapping targets were subjected to protein–protein interaction analysis using STRING and Cytoscape. Hub genes were identified based on degree centrality. miRNA–target interactions were analyzed using miRNet and miRTarBase. Functional enrichment analysis was performed through Gene Ontology and KEGG pathway analysis. Results: Key phytoconstituents including gingerol, shogaol, menthol, rosmarinic acid, hesperidin, limonene, and naringenin demonstrated interaction with multiple atherosclerosis-related targets. Core hub genes identified included TNF, IL6, AKT1, VEGFA, MAPK1, STAT3, ICAM1, and VCAM1. miRNA interaction analysis revealed regulatory association with miR-21, miR-146a, miR-155, miR-126, and miR-33, which are implicated in endothelial inflammation, lipid metabolism, macrophage activation, and vascular remodeling. Enrichment analysis indicated significant involvement of PI3K-Akt, NF-κB, MAPK, TNF, and lipid-atherosclerosis signaling pathways. Conclusion: The findings suggest that Sikkanchar Manapagu exerts potential anti-atherosclerotic activity through multi-component and multi-target modulation of inflammatory and lipid-associated miRNA signaling networks. This study provides a systems pharmacology basis for further experimental validation of Siddha formulations in cardiovascular diseases.

Keywords: Sikkanchar Manapagu, atherosclerosis, miRNA, network pharmacology, Siddha medicine, cardiovascular disease, bioinformatics.