<i>Clerodendrum infortunatum</i> (CI) Against Breast Cancer (BC) and Evaluating Its Cytotoxic Activity: A Combined In Silico and In Vivo Approach

ABSTRACT Background : Clerodendrum infortunatum (CI) is a traditional medicinal plant that is predominantly used in Ayurvedic and Siddha systems for the management of various human ailments due to a wide range of therapeutic potential through its diverse bioactive profile. Although it has been in use for several decades, its therapeutic potential against cancer (especially BC) is still far from fully unraveled. The present study aims at the evaluation of CI‐mediated cancer cell cytotoxicity using integrated in silico and in vivo approaches. Method : Phytochemical screening and GC–MS analysis for identifying active compounds from the methanolic extract of CI peel. The BC‐associated gene targets were obtained from the GeneCard and National Center for Biotechnology Information (NCBI) databases, and the compound targets were predicted by Swiss Target Prediction. Specific key genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using DAVID. PPI networks of the intersecting genes were constructed by the STRING database, and hub genes were then screened by Cytoscape software. QSAR modeling, pIC 50 prediction, and molecular docking to determine the potency and binding affinity of compounds. A brine shrimp lethality assay was performed to evaluate in vivo cytotoxicity. Result : Two‐seventy‐four overlapping targets were identified, of which the hub genes ESR1, BCL2, HSP90AB1, HIF1A, and SRC were significantly associated with BC. Molecular docking identified compounds with similar strong binding affinities, such as CID 13257219 and CID 117981. The brine shrimp assay has exhibited that the extract was moderately cytotoxic (LC 50 = 0.5735 mg/mL). Conclusion : CI displays potent anticancer effects against BC using molecular and cellular analyses. This suggests that further validation should be done through cancer cell line assays and molecular dynamics simulation studies to determine its therapeutic potential.