Anticancer Mechanism of Thalictrum punduanum Root Extract Against Breast and Colorectal Cancer: A Network Pharmacology and Molecular Docking Simulation Insights

Abstract

Thalictrum punduanum (locally known as Baduri) has traditionally been used in Nepal as a root decoction to combat cancer. This study aimed to investigate the anticancer mechanisms of T. punduanum root extract against breast and colorectal cancers using integrated network pharmacology and experimental approaches. LC-MS analysis was performed to identify phytoconstituents from a 70% methanolic extract of T. punduanum root. Active constituents were screened based on drug-likeness and ADME properties using the TCMSP and MolSoft platforms. Potential targets of these bioactives and cancer-related genes were retrieved from Swiss Target Prediction and GeneCards databases and intersected using Venny 2.1.0. Protein–protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway enrichment analyses were executed utilizing STRING, Cytoscape, and ShinyGO. Molecular docking and molecular dynamics simulations were conducted using the Molecular Operating Environment (MOE) software. Finally, anticancer effect was validated via in vitro MTT assays on breast and colorectal cancer cell lines. Ten phytoconstituents were identified, including four active alkaloids — coptisine, isoboldine, thalifendine, and berberine. PPI analysis highlighted AKT1, TP53, and SRC as central targets. GO analysis suggested that alkaloids may exert effects through cellular responses to reactive oxygen species, dendritic growth cone modulation, and nitric-oxide synthase regulation. KEGG pathway enrichment indicated that EGFR tyrosine kinase inhibitor resistance, ErbB signaling, and PI3K-AKT signaling are the key pathways involved in the anticancer effect. Molecular docking and molecular dynamics simulations demonstrated favorable binding affinities and stability of berberine and isoboldine with AKT1 and SRC, respectively. Moreover, in vitro assays revealed mild-moderate antioxidant and anticancer effects of T. punduanum root extract against breast and colorectal cancer cells. These findings provide preliminary insights into the phytochemistry of T. punduanum root extract and underscore its potential as an anticancer phytomedicine, justifying the further isolation of bioactive compounds and comprehensive cell line and in vivo studies.