Network pharmacology and molecular dynamics based elucidation of phytochemicals in colorectal cancer therapy.

Colorectal cancer (CRC) is also among the most common and deadly malignancies in the world, which requires the creation of safer and more efficient therapeutic options. , which has various pharmacological properties, was studied in its anti-CRC potential based on a detailed network pharmacology and molecular modelling study. Apigenin, Betulonic acid, b-ionone, Cosmosiin, d-borneol, and Hesperetin, six bioactive compounds, passed pharmacokinetics criteria and were associated with 155 targets of CRC. The analysis of protein-protein interaction revealed the major hub genes TNF-α, HSP90AA1, and ESR1. KEGG enrichment analysis identified major pathways related to CRC such as TNF-α signaling, PD-L1/PD-1 checkpoint, chemical carcinogenesis and thyroid hormone signaling. Molecular docking in molecular docking (average RMSD < 2.5 Å, Rg ≈ 20.2 Å). Betulonic acid (- 8.3 kcal/mol) and Cosmosiin (- 7.9 kcal/mol) were found to have high binding affinities with TNF-α, indicating their possible use in the regulation of tumor progression caused by inflammation. Their drug-likeness was supported by PK results of ADMET profiling that reported positive intestinal absorption (> 90%) and low toxicity levels. Besides, analysis of the expression showed that in advanced colon tumors, there were high levels of TNF-α (tumor necrosis factor-alpha) which were associated with a low survival rate. All of these quantitative results prove that has multi-target treatment potential against CRC. Although the computational forecast of the computational predictions suggests that TNF-α related signaling is a viable mechanistic pathway, they are still predictive and need to be further validated in wet-labs in order to confirm its clinical significance.