Exploring The Mechanism of Action of Curcuma longa and Phyllanthus niruri as Inflammatory Inhibitors in Cancer Via JAK3, STAT3, iNOS, and NF-κB Pathways Based on Computational Prediction

Abstract

The inflammatory response is triggered by various stimuli, including the precursor to carcinogenesis. Curcuma longa and Phyllanthus niruri are herbal that have anti-inflammatory activity. This study employed computational predictions, including molecular docking and molecular dynamics simulations. The protein targets for computational analysis included iNOS (PDB ID: 4NOS), JAK3 (PDB ID: 6NY4), STAT3 (PDB ID: 6NUQ), and NF-κB (PDB ID: 1NFI). The results showed that eriodictin exhibited the most potent binding affinity with target proteins, including JAK3, iNOS, NF-κB, and STAT3, with binding affinity values of -9.5, -10.1, -7.8, and -7.3 kcal/mol, respectively. The RMSD analysis for a 20 ns molecular dynamics simulation of NF-κB, iNOS, JAK3, and STAT3 protein complexes showed that the NF-κB–eriodictine complex reached stability within the 6–8 Å range after 10 ns, followed by increased fluctuations. A similar trend was observed in the NF-κB complex with the inhibitor, used as a control. Meanwhile, the RMSD of the iNOS–eriodictine complex stabilized at approximately 3 Å for 15 ns. The JAK3–eriodictine, STAT3–eriodictine, and STAT3–inhibitor complexes maintained stability within the 2–3 Å range throughout the simulation. The stability observed in these complexes suggests that eriodictine has potential as an effective therapeutic agent targeting NF-κB, iNOS, JAK3, and STAT3 proteins. Further studies, including in vitro and in vivo assays, are needed to validate these findings and assess their clinical applications. This study highlights the potential of Curcuma longa and Phyllanthus niruri derivatives as natural compound-based alternatives for managing chronic inflammation in cancer.