Unraveling the Multi-Targeted Anticancer Actions of Lepidium sativum L. via Network Pharmacology and Molecular Docking Insights

Lepidium sativum L. (garden cress) is a traditional medicinal plant rich in bioactive compounds including flavonoids, phenolic acids, polysaccharides, and glucosinolates. Although its anticancer activity has been reported, the molecular mechanisms underlying these effects remain largely unexplored. This study aimed to elucidate the anticancer mechanisms of L. sativum using an integrated in silico approach combining network pharmacology and molecular docking. Forty-two experimentally confirmed phytochemicals of L. sativum were retrieved from literature and subjected to ADME screening based on Lipinski's rule of five and oral bioavailability criteria. Potential protein targets were predicted using STITCH and UniProt databases, and interaction networks were constructed and analyzed using Cytoscape. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via the DAVID platform, while molecular docking simulations were carried out using the Schrödinger Maestro suite to validate key ligand–target interactions. The constituent–target network revealed 42 compounds interacting with 39 cancer-related proteins, with quercetin, apigenin, luteolin, resveratrol, and caffeic acid identified as core bioactive metabolites. Key target genes included ESR1, MMP9, CYP1A2, CYP1B1, and MMP2. Enrichment analyses suggested that L. sativum primarily affects metabolic and cancer pathways, as well as pathways related to arachidonic acid metabolism and PI3K-Akt signaling. Molecular docking showed strong binding affinities between the highlighted phytochemicals and cancer-related genes, particularly quercetin, which demonstrated significant interactions with multiple targets. Overall, this study provides insights into the anticancer mechanisms of L. sativum and underscores the potential of quercetin as a natural anticancer agent, warranting further research.