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Research Article

Revealing curcumin therapeutic targets on SRC, PPARG, MAPK8 and HSP90 as liver cirrhosis therapy based on comprehensive bioinformatic study

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Received 20 Aug 2023, Accepted 09 Dec 2023, Published online: 12 Jan 2024
 

Abstract

Cirrhosis naturally progresses through three stages: compensated, decompensated, and late decompensated, which carry an elevated risk of death. Although curcumin’s anti-cirrhosis effects have been studied, underlying mechanism in preventing cirrhosis progression and the correlation between curcumin’s action with upregulated genes remains insufficiently explored. In this study, we employed network pharmacology approach to construct a drug-target-disease network through bioinformatics and validate the findings with molecular docking and dynamic simulation. The curcumin-targeted liver cirrhosis network encompassed 54 nodes with 282 edges in protein-protein interactions (PPI) network. By utilizing network centrality analysis, we identified eight crucial genes. KEGG enrichment pathway revealed that these crucial genes are involved in pathway of cancer, endocrine resistance, estrogen signaling, chemical carcinogenesis-receptor activation, lipid metabolism, and atherosclerosis. Notably, these eight genes predominantly participate in cancer-related pathways. Further investigation revealed upregulation of four genes and downregulation of four others in hepatocellular carcinoma patients. These upregulated genes—MAPK8, SRC, PPARG, and HSP90AA1—strongly correlated with reduced survival probability in liver hepatocellular carcinoma patients with survival times approximately under 4000 days (∼11 years). Molecular docking and molecular dynamic results exhibited curcumin’s superior binding affinities and stability compared to native ligands of MAPK8, SRC, PPARG, and HSP90AA1 within 50 ns simulations. Moreover, MM-GBSA analysis showed stronger binding energy of curcumin to MAPK8, SRC, and HSP90AA1 than native ligand. In conclusion, this study provides valuable insights into curcumin’s potential mechanisms in preventing liver cirrhosis progression, specifically in HCC. These findings offer a theoretical basis for further pharmacological research into anti-HCC effect of curcumin.

Communicated by Ramaswamy H. Sarma

Acknowledgments

The authors thanks to The Institute for Research and Community Service, Universitas Muhammadiyah Kalimantan Timur and Nano Center Indonesia, for providing the facilities needed for this research.

Authors’ contributions

K.A.A.K.S. Writing—Original Draft, Collected Data, Investigation., K.A.A.K.S, and P.H.S. Design Methodology, Data Curation, Validation., P.H.S., M.M.J., A.G.A., E.M., and N.T.R., Writing—Review & Editing, Software, Conceptualization. P.H.S., P.M.K., and E.M: Supervision, Project Administration, Finalized the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Institute for Research and Community Service, Muhammadiyah University of East Kalimantan in the Final Assignment Lecturer and Student Collaboration Program (Grant ID: 200.10/LPPM/A.4/C/2023).

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