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Effect of hyaluronic acid: Mechanistic investigations via topological and functional analysis of its protein interaction network

Purpose: To predict molecular targets and the mechanism of action of hyaluronic acid against various disease conditions. Methods: The present study was designed and conducted based on the principle of network pharmacology, protein-protein interaction (PPI) database, and biological process analysis. At a high confidence score, a protein network comprising seventeen human protein targets was achieved from STITCH (Search Tool for Interaction of Chemicals). Results: Cytoscape-based protein-protein interaction network (PPIN) with 342 nodes was developed and analyzed to ascertain the molecular basis of hyaluronic acid actions. It revealed that hyaluronic acid was mainly involved in various physiological processes including extracellular matrix (ECM) disassembly, collagen catabolic process, mucopolysaccharide metabolic process, and circadian regulation of gene expression. Conclusion: The retrieved pathways are known to be involved in causing several pathologies such as leukemia, psoriasis, tick-borne encephalitis, etc. These pathways are influenced by hyaluronic acid. However, further explanations are required to elucidate whether these targets of hyaluronic acid have a therapeutic or toxicological role.