Abstract
Colorectal cancer (CRCs) is one of the prominent malignancies which ranks 2nd among all cancers worldwide in terms of mortality. Given the significant impact of CRC worldwide, the identification of effective drug for the treatment remains a considerable challenge. Oxalis genus especially Oxalis triangularis A. St.-Hil (OT) belonging to family Oxalidaceae, exerts numerous pharmacological effects, including anti-inflammatory, anti-oxidant and anti-bacterial effects. However, the mechanism underlying the effect of OT against CRC treatment remains unexplored. In this study, target identification was carried out using network pharmacology (NP). The top targets from NP were taken further for CDOCKER molecular docking with 131 phytoconstituents identified from OT by LC-MS and GC-MS analysis. The NP study revealed 3 important targets namely signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor 1 subunit alpha (HIF1A) and estrogen receptor 1 (ESR1). These three targets were utilized for docking studies for the lead identification. Top 5 phyto-constituents (lead) identified during docking had a docking score ranges from "- 62.2026 to - 50.167 kcal/mol" for STAT3, "- 79.9526 to - 58.4467 kcal/mol" for HIF1A, and "- 73.5511 to - 59.8775 kcal/mol" for ESR1 suggesting strong binding affinity of phyto-constituents with the target protein. Common amino acid interactions between STAT3 and HIF1A with top 5 phytoconstituents are GLU 638 and ILE 659, and common amino acid interaction between ESR1 and phytoconstituents are LYS 529 and LEU 525. Further, molecular dynamics simulations position the 6PSJ ligand as a high-affinity lead, 6NJS as a candidate for polypharmacological targeting, and 3HQU as a reference for refining smaller scaffolds. The present study revealed that OT exerts anti-cancer effects, by targeting multiple pathways, laying a theoretical background for its use as a therapeutic candidate for CRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00632-5.