Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

Abstract

Background: Liver cirrhosis is a life-threatening seqsuel of many chronic liver disorders of varying etiologies. In this study, we investigated protein targets of curcumin in liver cirrhosis based on a bioinformatics approach. Methods: Gene/protein associations with curcumin and liver cirrhosis were probed in drug–gene and gene–diseases databases including STITCH/DGIdb/DisGeNET/OMIM/DISEASES/CTD/Pharos and SwissTargetPrediction. Critical clustering groups (MCODE), hub candidates and critical hub genes in liver cirrhosis were identified, and connections between curcumin and liver cirrhosis-related genes were analyzed via Venn diagram. Interaction of hub genes with curcumin by molecular docking using PyRx-virtual screening tools was performed. Results: MCODE analysis indicated three MCODEs; the cluster (MCODE 1) comprised 79 nodes and 881 edges (score: 22.59). Curcumin database interactions recognized 318 protein targets. Liver cirrhosis genes and curcumin protein targets analysis demonstrated 96 shared proteins, suggesting that curcumin may influence 20 candidate and 13 hub genes, covering 81% of liver cirrhosis critical genes and proteins. Thirteen shared proteins affected oxidative stress regulation, RNA, telomerase activity, cell proliferation, and cell death. Molecular docking analysis showed the affinity of curcumin binding hub genes (Binding affinity: ΔG < −4.9 kcal/mol). Conclusions: Curcumin impacted on several critical liver cirrhosis genes mainly involved in extracellular matrix communication, focal adhesion, and the response to oxidative stress.